Stemcell Eu Research Projects

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Stem Cells

European research projects involving stem cells in the 6th Framework Programme

EUROPEAN COMMISSION

Stem CellsEuropean research projects involving stem cells in the 6th Framework Programme

Edited by: Gwennal Joliff-Botrel Pascale Perrin

European Commission - Directorate General for Research Life Sciences, Genomics and Biotechnologies for Health

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Table of content

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INTRODUCTION - Stem cells and European Union funded research Introduction and glossary UNDERSTANDING - Fundamental knowledge relevant to human healthCELLS INTO ORGANS DNA REPAIR EMBRYOMICS EPISTEM Functional genomics for development and disease of mesodermal organ systems DNA damage response and repair mechanisms Embryomics: reconstructing in space and time the cell lineage tree Role of p63 and related pathways in epithelial stem cell proliferation and differentiation and in rare EEC-related syndromes ESTOOLS Platforms for biomedical discovery with human ES cells EUCOMM The European Mouse Genome Mutagenesis Program EUGENE2 European network on functional genomics of type 2 diabetes EuReGene European renal genome project EURO-Laminopathies Nuclear envelope-linked rare human diseases: From molecular pathophysiology towards clinical applications EuroBoNet European network to promote research into uncommon cancers in adults and children: Pathology, biology and genetics of bone tumors EuroHear Advances in hearing science: from functional genomics to therapies EUROPEAN MCL NETWORK European Mantle Cell Lymphoma Network: Translational determination of molecular prognostic factors and pharmacogenomics in a European interdisciplinary collaboration EURYTHRON Molecular Control of Erythropoiesis EuTRACC European Transcriptome, Regulome and Cellular Commitment Consortium EVI-GENORET Functional genomics of the retina in health and disease FunGenES Functional genomics in engineered ES cells HeartRepair Heart failure and repair INTERDEVO Gene networks in cortical interneuron development: modeling interneuron function in health and disease LYMPHANGIOGENOMICS Genome-wide discovery and functional analysis of novel genes in lymphangiogenesis MCSCs Migrating cancer stem cells in breast and colon cancer MSCNET Myeloma stem cell Network. A translational programme identifying and targeting the early myeloma cell hierarchy MUGEN Integrated functional genomics in mutant mouse models as tools to investigate the complexity of human immunological disease MYORES Multi-organismic approach to study normal and aberrant muscle development, function and repair ONCASYM Cancer stem cells and asymmetric division Plurigenes Pluripotency associated genes to de-differentiate neural cells into pluripotent cells REGULATORY GENOMICS Advanced genomics instruments, technology and methods for determination of transcription factor binding specificities; applications for identification of genes predisposing to colorectal cancer SIROCCO Silencing RNAs: organisers and coordinators of complexity in eukaryotic organisms THE EPIGENOME Epigenetic plasticity of the genome TRANSCODE Novel tool for high-throughput characterization of genomic elements regulating gene expression in chordates

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DEVELOPING - Tools for new therapies and medicinesAnti-tumor targeting CONSERT CRYSTAL E.E.T.-Pipeline EPI-VECTOR EURO-THYMAIDE EuroCSC EUROSTEMCELL EUROXY EVGN GIANT INTHER KIDSTEM Modulation of the recruitment of vessels and immune cells by malignant tumors: Targeting of tumor vessels and triggering of anti-tumor defense mechanisms Concerted safety & efficiency evaluation of retroviral transgenesis in gene therapy of inherited diseases CRYo-banking of Stem cells for human Therapeutic AppLication European Embryonal Tumor Pipeline Episomal vectors as gene delivery systems for therapeutic applications Novel approaches to pathogenesis, diagnosis and treatment of autoimmune diseases based on new insights into thymus-dependent self-tolerance Targeting cancer stem cells for therapy European consortium for stem cell research Targeting newly discovered oxygen-sensing cascades for novel cancer treatments: Biology, equipment, drug candidates European Vascular Genomics Network Gene therapy: an integrated approach for neoplastic treatment Development and application of transposons and site-specific integration technologies as non-viral gene delivery methods for ex vivo gene-based therapies Developing a Stem Cell Based Therapy to Replace Nephrons Lost through Reflux Nephropathy 1 1 1 1 1 1 1 1 1 1 1 1 1

4143 44 45 46 47 48 49 50 51 52 53 54 55

magselectofection MODEST MOL CANCER MED MYOAMP NEURONE NEUROscreen NSR OsteoCord SKINTHERAPY STEM-HD STEMS SyntheGeneDelivery TherCord TUMOR-HOST GENOMICS X-ALD

Combined isolation and stable nonviral transfection of hematopoietic cells ? a novel platform technology for ex vivo hematopoietic stem cell gene therapy Modular devices for ultrahigh-throughput and small volume nucleofection Developing molecular medicines for cancer in the post genome era based on telomerase and related telomere-maintenance mechanisms as targets Amplification of human myogenic stem cells in clinical conditions Molecular mechanisms of neuronal degeneration: from cell biology to the clinic The Discovery of Future Neuro-therapeutic Molecules Nervous System Repair Bone from blood: Optimised isolation, characterisation and osteogenic induction of mesenchymal stem cells from umbilical cord blood Gene therapy for Epidermolysis Bullosa: a model system for treatment of inherited skin diseases Embryonic stem cells for therapy and exploration of mechanisms in Huntington Disease Pre-clinical evaluation of stem cell therapy in stroke Ex vivo gene delivery for stem cells of clinical interests using synthetic processes of cellular and nuclear import and targeted chromosomal integration Development and preclinical testing of cord blood-derived cell therapy products Genome-wide analysis of signaling pathways in regulation of the interactions between tumor and host cells: Applications for cancer therapy X-linked adrenoleukodystrophy (X-ALD): pathogenesis, animal models and therapy

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BUILDING - Tissue engineering3G-SCAFF AUTOBONE BARP+ BIOSYS CellPROM CORNEA ENGINEERING Custom-IMD EXPERTISSUES GENOSTEM HIPPOCRATES LIVEBIOMAT NANOBIOCOM NanoEar NEWBONE SILKBONE SmartCaP STEPS VASCUPLUG Third generation scaffolds for tissue engineering & regenerative medicine Production unit for the decentralised engineering of autologous cell-based osteoinductive bone substitutes Development of a bioartificial pancreas for type I diabetes therapy - nanotechnology biomaterial engineering transplantation Intelligent biomaterial systems for cardiovascular tissue repair Cell programming by nanoscaled devices Three-dimensional reconstruction of human corneas by tissue engineering SME supply chain integration for enhanced fully customisable medical implants, using new biomaterials and rapid manufacturing technologies, to enhance the quality of life for eu citizens Novel therapeutic strategies for tissue engineering of bone and cartilage using second generation biomimetic scaffolds Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side A hybrid approach for bone and cartilage tissue engineering using natural origin scaffolds, progenitor cell and growth factors Development of new polymeric biomaterials for in vitro and in vivo liver reconstruction Intelligent nanocomposite for bone tissue repair and regeneration 3g-Nanotechnology based targeted drug delivery using the inner ear as a model target organ Development of load-bearing fibre reinforced composite based non-metallic biomimetic bone implants Development and evaluation of mineralized silk based composites for orthopaedic applications Injectable macroporous biomaterial based on calcium phosphate cement for bone regeneration A systems approach to tissue engineering processes and products - biomaterial engineering biomedical engineering nanotechnology Bioreactive composite scaffold design for improved vascular connexion of tissue-engineered products

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MODELLING - Mathematical & biology models, alternatives to animals testingARTEMIS CARCINOGENOMICS CONTROL CANCER STEM INVITROHEART M3CS-TU TH NEURO PREDICTOMICS ReProTect VITROCELLOMICS In Vitro Neural Tissue System For Replacement Of Transgenic Animals With Memory / Learning Deficiencies Development of a high throughput genomics-based test for assessing genotoxic and carcinogenic properties of chemical compounds in vitro Developing a virtual and molecular control board for diverting cancer stem cell to nonmalignance Reducing Animal Experimentation in Drug Testing by Human Cardiomyocyte In Vitro Models Derived from Embryonic Stem Cells Modeling, Mathematical Methods and Computer Simulation of Tumour Growth and Therapy Towards the neuronal machine Short-term in vitro assays for long-term toxicity Development of a novel approach in hazard and risk assessment or reproductive toxicity by a combination and application of in vitro, tissue and sensor technologies Reducing Animal Experimentation in Preclinical Predictive Drug Testing by Human Hepatic In Vitro Models Derived from Embryonic Stem Cells

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REPAIRING - Towards clinical applications for diseases and impairementsBETACELLTHERAPY EuroSTEC MYOCARDIAL REPAIR RESCUE SC&CR STEMSTROKE STROKEMAP THERAPEUSKIN Ulcer Therapy Beta cell programming for treatment of diabetes Soft tissue engineering for congenital birth defects in children: new treatment modalities for spina bifida, urogenital and abdominal wall defects Clinical experience with bone marrow cells and myoblasts transplantation for myocardial repair From stem cell technology to functional restoration after spinal cord injury Application and process optimization of human stem cells for myocardium repair Towards a stem cell therapy for stroke Multipotent Adult Progenitor Cells to treat Stroke Ex vivo gene therapy for recessive dystrophic epidermolysis bullosa: pre-clinical and clinical studies Gene transfer in skin equivalents and stem cells: novel strategies for chronic ulcer repair and tissue regeneration

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TREATING - Improvement of standard hematopoeitic stem cell transplantationALLOSTEM The development of Immunotherapeutic strategies to treat haematological and neoplastic diseases on the basis of optimised allogeneic stem cell transplantation CLINT Facilitating International Prospective Clinical Trials in Stem Cell Transplantation EUROPEAN LEUKEMIA NET Strengthen and develop scientific and technological excellence in research and therapy of leukemia (CML, AML, MDS, CLL, adult ALL) by cooperation and integration of the leading national leukemia networks and groups in Europe FIRST Further improvement of radiotherapy of cancer through side effect reduction by application of adult stem cell therapy RISET Reprogramming the immune System for the Establishment of Tolerance STEMDIAGNOSTICS The development of new diagnostic tests, new tools and non-invasive methods for the prevention, early diagnosis and monitoring for haematopoietic stem cell transplantation TRANS-NET Identification of genomic and biological markers as predictive/diagnostic/therapeutic tools for use in allogeneic stem cell transplantation: Translational research towards individualised patient medicine TRIE Transplantation Research Integration across Europe

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INTEGRATING - Ethics, legal, societal aspects, trainingEMRS EU hESC registry EUROCITS imgbchimerashybrids INDUSTRYVECTORTRAIN INVIVOVECTORTRAIN REPROGENETICS SENECA StemCellPatents Worldwide study A European multimedia repository of science - video 1: stem cells to repair the heart European human embryonic stem cell registry Europe, its citizens and stem cell research: a one-day conference Chimeras and hybrids in comparative European and international research scientific, ethical, philosophical and legal aspects European labcourse: Advanced methods for industrial production, purification and characterisation of gene vectors European labcourse: Towards clinical gene therapy: preclinical gene transfer assessment Reprogenetics: the ethics of men making men From Cellular Senescence and Cell Death to Cancer and Ageing Stem cell patents: European patent law and ethics A worldwide study of umbilical cord cell banking

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Introduction and glossary ANNEX - Classification of projects by tissues, organs and diseases

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INTRODUCTION

STEM CELLS

What are stem cells ?Tissues and organs in the body are made of specialised cells that assure their specific functions. Maintenance and repair of these tissues and organs depend upon resident unspecialised adult stem cells. They are still at an early stage of development and retain the potential to turn into the different types of cells of that tissue or organ. In bones, some typical adult stem cells, the bone marrow stem cells, give rise to all kinds of blood cells. Apart from those of the blood cell lineage, other stem cells are found in the bone, which are able to mature into cells specific to bone, cartilage, fat, tendons, muscle and heart. During pregnancy, cells from bone marrow of the developing foetus find their way into the umbilical cord and placenta. Research suggests that umbilical cord blood stem cells, less mature than those from adult bone marrow, might be induced to turn into non-blood cells. The only cells that can evolve into any cells in the body are found in few day-old fertilised eggs, and are called embryonic stem cells.

Stem cells are crucial for a healthy organismStem cells play a central role in the normal growth and development of animals and humans. They have three properties that distinguish them from other cell types and make them interesting to scientists: - they are unspecialised - they are able to divide and produce copies of themselves - they have the potential to produce other cell types.

Stem cells are central to many research areasStem cells provide an ideal model to understand the development of organisms under healthy and disease condition. It should help decrease animal use. Stem cells are expected to offer means to develop new families of drugs and new therapies: harnessing cell specialisation will lead to regenerative medicine. Stem cells are daily used to treat cancer: bone marrow grafts have been used against leukemias for 30 years. Research is done to extent this approach. Stem cells are experimentally used to repair injured organs or to fix degenerative diseases. They are injected into the body, often after being modified. Stem cells are used to build new tissues outside the body, to be grafted, or used for toxicology testing. Applications are now scarce but are expected to grow.

Research needs to study stem cells of all originsEach type of stem cell (adult, foetal and embryonic), in humans and animals, is a glance at a different moment of a global dynamic process. Only a partial knowledge can be expected from research done on one type of stem cells.

The use of some stem cells is a matter of debateResearch on human embryonic stem cells, a tiny part of the overall research on stem cells, raises several ethical issues. They are addressed by national legislation worldwide.

THE EUROPEAN UNION AND STEM CELLSThe European Union funds projects involving stem cellsThe European Union funds collaborative research projects, under the 6th Framework Programme (2002-2006). In several fields of research, some of the funded projects involve stem cells, either studying stem cells themselves, or using them as discovery means or biological tools in a broader context.

The 6th Framework Programme: five kind of projects for complementary objectivesIntegrated Projects (IP) adress major needs of society, by delivering knowledge for new products, processes or services Networks of excellence (NoE) use networking to overcome European research fragmentation in defined domains, strengthening and spreading scientific and technological excellence at the European level Specific Targeted Research Projects (STREP) focuses on very specific issues, to gain knowledge or improve existing products, processes or services, or demonstrate the viability of new technologies Coordinated actions (CA) co-ordinate research organisations, initiatives or projects for a specific purpose Specific Support Actions (SSA) support the Framework Programme, through events, networks, studies, stimulations of innovation..., or help building future Community research policies.

The 6th Framework Programme: research and discovery at the service of the whole societyAcademic organisations, corporates, individual scientists, members of the civil society, can be partners of a FP6 project. Participation of industry (IND), in particular of Small and Medium-sized Entreprises (SMEs), is highly encouraged, as it is essential that discoveries are transformed into products or services able to improve well being and health of people. In addition, a dynamic and innovative private sector is crucial for the European Union economy and employment.

A CATALOGUE OF EU-FUNDED PROJECTS

All the listed projects in this book have at least one component of stem cell research, or use stem cells as research tools. Projects which only use stem cells as non-specific tools, in particular to create animal models, are nevertheless not included, since such techniques are used by almost all life science laboratories on a daily basis.

From basic research to society: organisation of the projects in the catalogueWe chosed to organise the FP6 projects related to stem cells in a way reflecting the discovery process: understanding the biological issues, building tools (conceptual and technological), using knowledge and tools for clinical applications, and involving the whole society in the process. There is thus seven chapters in the book: UNDERSTANDING: fundamental knowledge relevant to human health DEVELOPING: tools for new therapies and medicines BUILDING: tissue engineering MODELLING: mathematical & biological models, and alternatives to animal testing REPAIRING: preclinical & clinical studies for diseases and impairments TREATING: improvement of standard hematopoietic stem transplantation INTEGRATING: ethics, legal & societal aspects, training

Organising the projects by their relevance to tissues, organs and diseasesAs we appreciate that some people, in particular patients and medical doctors, can also be interested by a more clinicaloriented classification of the projects, we have added at the end of the book a list of projects per type of tissue (following their embryological origin). We also listed the projects concerning cancers and rare diseases. In the pdf version of the book, this cross-cutting classification is a second way of accessing the projects through the bookmarks. Indeed, in addition to the table of content listing all the projects according to the research process, a second table of content lists the projects following this clinical approach, with clickable links to the projects.

UNDERSTANDING Fundamental knowledge relevant to human health

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CELLS INTO ORGANS: FUNCTIONAL GENOMICS FOR DEVELOPMENT AND DISEASE OF MESODERMAL ORGAN SYSTEMSProposal acronym Contract n Duration (starting date) CELLS INTO ORGANS LSHM-CT-2004-504468 5 years (01.04.04) EC contribution () Instrument Participants 7.200.000 NoE 12

Abstract:The development of new approaches to treating disease will revolutionise health care in the coming decade. Treatment of cancers will increasingly rely on targeted molecules rather than cytotoxic drugs. Manipulation of stem cells for cell and tissue replacement therapies holds great promise for treatment of degenerative disease and injury. Both approaches depend critically on detailed knowledge of the molecular and cellular events governing normal differentiation of the target organs and tissues. This knowledge provides the basis for organ and tissue engineering. Many important diseases affect organ systems such as heart, vascular system, blood, kidneys, skeleton, and musculature- deriving substantially or exclusively from mesodermal cells. Heart failure and strokes resulting from atherosclerosis, kidney failure, muscular dystrophy, osteoporosis, tumours and leukaemia are caused either by defects in development of these mesoderm containing organ systems or in their function, frequently as a consequence of ageing. Together, these diseases represent principal obstacles to reaching a healthy old age. This is a very important area of research where there is a great need to integrate resources. The area suffers from fragmentation. Different subjects are isolated Different experimental systems, each useful for a particular limited spectrum of experimental approaches have led to different and sometimes conflicting views. Few groups access the possibilities offered by combining approaches in different experimental organisms and few have attempted to integrate findings made in different species using different techniques. While some groups have developed important technology with potentially wide applicability or have access to powerful resources, the technology and resources are not widely applied but usually used only by a small circle. This applies notably to the recent advent of high throughput techniques and availability of related facilities like microarrays. Fourth, too few scientists think in a multi-problem, multi- system or multitechnical way. This indicates the need to train a new generation of young researchers. The primary purpose of this network is to develop an integrated approach to research into mesodermal organ systems. This network will elucidate molecular and cellular processes underlying specification and differentiation of mesodermally derived organ systems. It integrates developmental genetics and experimental embryology with modern cell biology and genome scale analysis. These new technologies will enable to identify genes which function in building a specific organ or in a particular aspect of embryogenesis. A major revelation of developmental biology has been the extent to which molecular strategies are redeployed, even during regeneration. Thus this information is the basic knowledge required for organ and tissue engineering. It is, however, a task which will far exceed the capacity or expertise of any one research group, and which requires the complementary advantages of different vertebrate and invertebrate systems and the combination of multidisciplinary skills, necessitating collaboration. This network integrates twenty four leading European groups in twelve renowned centres of excellence into the world's leading network for investigating the development and disease of mesodermal organ systems. Each of our major groups is a world leader in investigating a specific aspect of the development of mesoderm or a key mesodermal organ system or in applying a key genomic technique.

Web site:

http://www.cellsintoorgans.net

Participants:Coordinator Netherlands Austria France Germany Italy Netherlands Portugal Switzerland United Kingdom Profs. Anthony John Durston, Jacqueline Deschamps & Rik Korswagen, Hubrecht Laboratory / Netherlands Institute for Developmental Biology , Utrecht tel: +31 30 2121 800 / 977 fax: +31 30 2516 464 Tony@niob.knaw.nl Erwin Wagner & Christine Hartmann, Research Institute of Molecular Pathology, Vienna Margaret Buckingham & Jean-Franois Nicolas, Institut Pasteur, Paris Herbert Jaeckle, Max Planck Gesellschaft, Mnchen Guilio Cossu, Fondazione Centro San Raffaele Del Monte Tabor, Stem Cell Res. Inst., Milan Frank Grosveld, Elaine Dzierzak & Jeroen Charite, Erasmus Univ. Medical Center, Rotterdam Antonio Jacinto & Isabel Palmeirim-Thorsteinsdottir, Instituto Gulbenkian de Ciencia, Oieras Walter Gehring & Markus Affolter, Biozentrum, University of Basel Denis Duboule, University of Geneva, Dept of Zoology Jim Smith & John Gurdon, The Chancellor, Masters & Scholars of the University of Cambridge Philip Ingham, Anne-Gaelle Borycki & Henry Roehl, School Med. Biomedical Sci., Univ. Sheffield Claudio Stern & Lewis Wolpert, University College London

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

DNA DAMAGE RESPONSE AND REPAIR MECHANISMSProposal acronym Contract n Duration (starting date) DNA REPAIR LSHG-CT-2005-512113 4 Years (01.05.05) EC contribution () Instrument Participants 11.500.000 IP 16

Abstract:This integrated project focuses on unravelling mechanisms of DNA damage response and repair, an area with a major impact on human health, notably cancer, immunodeficiency, other ageing related- diseases and inborn disorders. The proposal brings together leading groups with multi-disciplinary and complementary expertise to cover all pathways impinging upon genome stability, ranging from molecules to mouse models and human disease. Objectives: The main objective is to obtain an integrated perception of the individual mechanisms, their complex interplay and biological impact, using approaches ranging from structural biology to systems biology. Translation of the results that we obtain is expected to contribute to an improved quality of life through (1) possible identification of genetic markers for assessment of susceptibility to occupational hazards and disease, (2) discovery of promising targets for therapy, (3) improved diagnostic and prognostic procedures for genetic disorders, (4) early diagnosis and prevention of cancer and other ageing-related diseases. We have also included a strong training component in the project to invest in young talented students, who may become the leaders of tomorrow. Approach: The pleiotropic effects inherent to the time-dependent erosion of the genome and the complexity of the cellular responses to DNA damage necessitate a comprehensive, multidisciplinary approach, which ranges from molecule to patient. At the level of structural biology and biochemistry, individual components and pathways will be analysed to identify new components and clarify reaction mechanisms. The interplay between pathways and cross-talk with other cellular processes will be explored using both biochemical and cellular assays. To better understand the function and impact of DNA damage response and repair systems in living organisms, we will take full advantage of our existing unique and extensive collection of models.

Web site:

http://www.erasmusmc.nl/dna-repair

Participants:Coordinator Netherlands Denmark France Germany Ireland Italy Netherlands Norway Switzerland United Kingdom Prof. Jan H.J. Hoeijmakers, Erasmus Medical Center Rotterdam tel: +31 104 087 199 fax: +31 104 088 468 j.hoeijmakers@erasmusmc.nl Jiri Bartek, Danish Cancer Society, Copenhagen Jean-Marc Egly, Centre Europeen pour la Recherche en Biologie et Medecine, Illkrich Karl-Peter Hopfner, Ludwig-Maximilians-Universitat Munchen Noel F. Lowndes, National university of Ireland, Galway Marco Foiani, IFOM, Istituto FIRC di Oncologia Molecolare, Milan Paolo Plevani, Universita degli Studi di Milano, Milan Leon Mullenders, Leiden University Medical Center, Division 5, Leiden Hans Einar Krokan, Norwegian University of Science and Technology, Trondheim Erling C. Seeberg, University of Oslo, Rikshospitalet, Oslo Josef Jiricny, University of Zurich Stephen Philip Jackson, The Chancellor, Masters and Scholars of the University of Cambridge Alan Robert Lehmann, University of Sussex, Falmer, Brighton Stephen West, Cancer Research UK, London Graeme Cameron Murray Smith, KuDOS Pharmaceutical Limited, Cambridge, SME

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

EMBRYOMICS: RECONSTRUCTING IN SPACE AND TIME THE CELL LINEAGE TREEProposal acronym Contract n Duration (starting date) EMBRYOMICS FP6-2003-NEST-B1-012916 3 years (01.11.05) EC contribution () Instrument Participants 1.449.850 NEST-ADVENTURE 4

Abstract:Embryomics is devoted to the morphodynamical reconstruction of the cell lineage tree underlying the processes of animal embryogenesis. We will design a set of strategies, methods and algorithms to sequence the cell lineage tree as a branching process annotated in space and time. We view this highly interdisciplinary project as the foundation of a new scientific field that we call Embryomics with a reference to Genomics. In the same sense as Genomics, Embryomics is both a scientific field and a technology to gather data with a lot of potential applications. But the Embryomics data is much more complex than a mere DNA sequence as it does not appear as a linear static information in one dimension but as a branching dynamical process displayed in space and time. To deal with this information, we undertake a highly novel and most promising approach based on the strategies of the mammalian visual system. Our goal is to fully reconstruct the dynamics of cell divisions and movements from time-lapse series of high-resolution optical sections obtained by multiphoton laser scanning microscopy throughout embryonic development of live animals. Embryomics will allow the automated tracking of events such as cell division and cell death in live embryos and give us access to parameters such as the rate of cell proliferation in time and space. This kind of data is highly relevant to investigate stem cell populations, early steps of cancerogenesis and drug effects in vivo. The post-genomic era needs such a systematic approach at the level of the cellular organization to achieve an integrated understanding of biological processes. In addition, through the investigation of four different organisms with key phylogenetic positions, we aim at promoting the use of non-mammalian animal models. A comparative Embryomics strategy is the best way to evaluate the relevance of animal models, whatever their evolutionary distance to human, for further medical applications.

Web site:

http://complexsystems.lri.fr/Embryomics/tiki-index.php

Participants:Coordinator France Dr. Nadine Peyriras, CNRS / UPR2297, Development Evolution Plasticity of the Nervous System, Institut de Neurobiologie Alfred Fessard, Gif-sur-Yvette Prof. Paul Bourgine, CNRS / Ecole Polytechnique UMR7656, Centre Research in Applied Epistemology, Paris tel: +33 1 44 32 39 55 fax: +33 1 44 32 39 88 peyriera@inaf.cnrs-gif.fr Jean-Franois Nicolas, Molecular Biology Development Unit, Institut Pasteur, Paris Alessandro Sarti, Department of Electronics, Information and Systems, University of Bologna Karol Mikula, Department of Mathematics and Descriptive Geometry / Faculty of Civil Engineering, Slovak University of Technology, Bratislava

France Italy Slovakia

Commission: Directorate General for Research - Idea programme Directorate - Unit S2

ROLE OF P63 AND RELATED PATHWAYS IN EPITHELIAL STEM CELL PROLIFERATION AND DIFFERENTIATION AND IN RARE EEC-RELATED SYNDROMESProposal acronym Contract n Duration (starting date) EPISTEM LSHB-CT-2005-019067 4 years (01.01.06) EC contribution () Instrument Participants 2.500.000 IP 10

Abstract:The focus of EPISTEM is to generate new knowledge and translate it into applications that enhance human health. To this end both fundamental and applied research will be involved. `EPISTEM? integrates multidisciplinary and coordinated efforts to understand the molecular basis of factors involved in epidermal stem cell generation, maintenance and differentiation and skin disease. Moreover, the core molecule that will be studied in this IP is p63 (and related pathways), a molecule genetically proven to be involved in the development of rare skin diseases such as EEC syndrome, Hay-Wells (AEC) syndrome, Limb-mammary syndrome, ADULT syndrome, Rapp-Hodgkin syndrome and non-syndromic split handsplit foot malformation. Collectively, the prevalence of ectodermal dysplasia syndromes (EDS) is estimated at 7 cases in 10,000 births. Currently there is no cure for these patients. By creating the `EPISTEM? consortium we want to address from different angles (genetics, gene profiling, molecular and cellular biology, structural biology, drug desing), the molecular pathways involved in epidermal dysplasia syndromes making use of different technologies (mutation analysis, micro-array, ChiP, transgenes, proteomics, in vitro skin cultures, crystallography, etc). Our consortium brings together leading European clinicians, geneticists, molecular and cellular biologists, structural biologists and a drug designer in the field of p63 (and related molecules) research. Therefore, this research fits in the centre of the specific topic "Exploring the potential of stem cells and/or primary cells for the understanding of monogenic rare diseases and the development of new drugs for their treatments".

Web site:

http://www.epistem.eu/

Participants:Coordinator Belgium France Germany Italy Prof. Peter Vandenabeele, Department for Molecular Biomedical Research, Faculty of Sciences, VIB-University Ghent, Flanders Interuniversity Institute for Biotechnology VZW, Gent-Zwijnaarde tel: +32 (0) 9 33 13 760 fax: +32 (0)9 33 13 609 peter.vandenabeele@dmbr.Ugent.be Daniel Aberdam, U634, Institut National de la Sante et de la Recherche Medicale, Nice Volker Dtsch, Institute for Biophysical Chemistry, J. W. Goethe-Universitt Frankfurt am Main, Frankfurt / Main Roberto Mantovani, Dipartimento di Scienze Biomolecolari e Biotecnologie, Universit degli Studi di Milano, Milano Alessandro Terrinoni, Biochemistry Laboratory, IDI Farmaceutici SrL, Rome, Pomezia Gerry Melino, Biochemistry laboratory, University of Rome Tor Vergata Department of Experimental Medicine and Biochemical Sciences, Rome, SME Hans van Bokhoven, Div. Molecular Genetics, Dept. of Human Genetics, Univ. Medical Centre Nijmegen, Stichting Katholieke Universiteit, the University Medical Centre Nijmegen, Nijmegen Klas Wiman, Dept. of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm Gian-Paolo Dotto, Department of Biochemistry, University of Lausanne, Epalinges, Lausanne John McGrath, King's College London, Genetic Skin Disease Group, King's College London, London

Netherlands Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

PLATFORMS FOR BIOMEDICAL DISCOVERY WITH HUMAN ES CELLSProposal acronym Contract n Duration (starting date) ESTOOLS LSHG-CT-2006-018739 5 years (01.05.2006) EC contribution () Instrument Participants 12.000.000 IP 18

Abstract:The pluripotent nature of human embryonic stem (hES) cells presents unprecedented opportunities for studying human cellular differentiation and pathogenesis. Furthermore, hES cells offer a new resource for cellular transplantation in human degenerative disease and a powerful platform for pharmaceutical and toxicology screening. The promise of hES cells rests largely on achieving two things: (i) unlimited expansion in stem cell numbers without genetic or epigenetic compromise; (ii) directing differentiation with absolute phenotypic fidelity. Delivery of these twin objectives entails full understanding of the mechanisms that control the choices between proliferation and self renewal on the one hand, and apoptosis and commitment to differentiation on the other. Genetic intervention will be a central tool in delineating the molecular circuitry of hES cells. The goal of ESTOOLS is to develop and implement the necessary tools to elucidate the genetic and molecular networks that control the self renewal, commitment and terminal differentiation of hES cells. Neural commitment provides a paradigm for understanding the mechanisms by which ES cells choose between self renewal and lineage commitment. Furthermore, neuronal and glial differentiation of hES cells offer major new experimental avenues for cellular neurobiology and pathogenesis, with the potential for application in pharmaceutical and toxicological screening and cell replacement therapies. ESTOOLS draws together a team of high quality researchers with complementary expertise in mouse ES cell systems, human ES cell culture, epigenetics, neurodevelopment, and a range of genetic modification technologies. ESTOOLS will create a range of training opportunities and dissemination vehicles to transfer knowledge and experience within the European Research Area.

Web site:

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Participants:Coordinator United Kingdom Czech Republic Finland Germany Israel Italy Netherlands Spain Sweden Switzerland United Kingdom Prof. Peter Walter Andrews, Department of Biomedical Science, University of Sheffield tel: +44-114-2224173 fax: +44-114-2222399 p.w.andrews@sheffield.ac.uk Petr Dvorak, Department of Molecular Embryology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Brno Timo Otonkoski, Faculty of Medicine, Developmental and Reproductive Biology Research Program, Helsingin yliopisto, University of Helsinki Riitta Lahesmaa, Turku Centre for Biotechnology, University of Turku Francis Stewart, Biotec, Genomics, University of Technology Dresden, Dresden Oliver Brstle, Institute of Reconstructive Neurobiology, Bonn Medical Center, Rheinische Friedrich Wilhelms Universitt Bonn, Rheinische Friedrich Wilhelms Universitt Bonn Dan Pines, stem cell technologies ltd., Jerusalem, SME Nissim Benvenisty, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem Elena Cattaneo, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, Faculty of Pharmacy, Universita' degli Studi di Milano, Milan Maarten van Lohuizen, Division of Molecular Genetics, The Netherlands Cancer Institute, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam Manel Esteller, Molecular Pathology Programme, Spanish National Cancer Centre, Cancer Epigenetics Laboratory, Fundacin Centro Nacional de Investigaciones Oncolgicas Carlos III, Madrid Gran Hermern, Department of Medical Ethics, Faculty of Medicine, Lund University, Lund Outi Hovatti, Karolinska Institutet, Karolinska Institutet, Stockholm Yves-Alain Barde, Pharmacology/Neurobiology, Biozentrum, University of Basel Paul Gerskowitch, Department of Biomedical Science, Axordia Ltd, Sheffield, SME Austin Gerard Smith, MRC Centre Development in Stem Cell Biology, Institute for Stem Cell Research, The University of Edinburgh Timothy E. Allsopp, Stem Cell Sciences UK Ltd, Edinburgh, SME Tariq Enver, MRC Molecular Haematology Unit, Medical Research Council, Headington, Oxford

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

THE EUROPEAN MOUSE GENOME MUTAGENESIS PROGRAMProposal acronym Contract n Duration (starting date) EUCOMM LSHM-CT-2005-018931 3 years (01.01.06) EC contribution () Instrument Participants 13.000.000 IP 11

Abstract:The EUCOMM integrated project responds to the priority topic defined by Priority 1. Life Sciences and Biotechnology for Health, ?Genome-wide Mutagenesis in Mouse?. EUCOMM integrates European skills, efforts, resources, and infrastructure to produce, in a systematic high throughput way, mutations throughout the mouse genome. A collection of up to 20000 mutated genes will be generated in mouse embryonic stem (ES) cells using conditional gene trapping and gene targeting approaches. This library will enable mouse mutants to be established worldwide in a standardized and cost-effective manner, making mouse mutants available to a much wider biomedical research community than has been possible previously. For a subset of genes believed to be relevant for human disease, mutant mice will be established, archived and analyzed. This will offer an opportunity to decipher molecular disease mechanisms and in some cases provide a foundation for the development of diagnostic, prognostic and therapeutic strategies. This project is built on exceptionally strong European expertise in mouse molecular genetics, genomics and bioinformatics and involves an SME which will enable automation of targeting vector production. EUCOMM will foster integration with existing European consortia which address mouse gene expression analysis, mutant phenotyping, imaging and archiving. Progress of all of these projects will be enhanced by the mouse mutants produced by EUCOMM. All targeting vectors, mutant ES cells, mouse resources, and Standard Operating Procedures generated by EUCOMM will be displayed to the scientific community via the EUCOMM web linked database, other EU consortia databases or the Ensembl browser and distributed by a professional distribution organization. Taken together, EUCOMM will make a major contribution to the analysis of gene function. Finally, EUCOMM resources represent major opportunities for exploitation by SMEs and the pharmaceutical industry.

Web site:

http://www.eucomm.org

Participants:Coordinator Germany France Germany Prof. Wolfgang Wurst, Institute of Developmental Genetics, GSF-National Research Center for Environment and Health, GmbH, Neuherberg tel: +49-89-31874110 fax: +49-89-31873099 wurst@gsf.de & cornelia.kaloff@gsf.de Pierre CHAMBON, Institut Clinique de la Souris, Centre Europeen de Recherche en Biologie et Medecine - Groupement d'Interet Economique, Illkirch Bernhard, Korn, Research, Development & Services / Compound Heidelberg, RZPD - Deutsches Ressourcenzentrum fur Genomforschung GmbH, Heidelberg, SME Harald von Melchner, Laboratory for Molecular Heamatology, Johann Wolfgang Goethe University Medical School, Frankfurt am Main Patricia Ruiz, Max Planck Institute for molecular Genetics, Department Lehrach, Max Planck Society for the Advancement of Science, Berlin Francis Stewart, Biotec Genomic, Technische Universitaet Dresden Gary Stevens & Harald Kranz, Gene Bridges GmbH, Heidelberg, SME Nadia, Rosenthal, EMBL Programme in Mouse Biology, European Molecular Biology Laboratory, Rome / Heildelberg Glauco Tocchini-Valentini, Consiglio Nazionale delle Ricerche - Istituto di Biologia Cellulare, Consiglio Nazionale delle Ricerche - Istituto di Biologia Cellulare, Monterotondo Scalo Allan Bradley, Wellcome Trust Sanger Institute, Genome Research Limited, Hinxton, Cambridge Steve Brown, MRC Mammalian Genetics Unit, Medical Research Council, Harwell, London

Italy United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

EUROPEAN NETWORK ON FUNCTIONAL GENOMICS OF TYPE 2 DIABETESProposal acronym Contract n Duration (starting date) EUGENE2 LSHM-CT-2004-512013 4 Years (01.11.04) EC contribution () Instrument Participants 8.000.000 NoE 13

Abstract:EUGENE2 is a well focused, cohesive and multidimensional effort whereby top European laboratories, together with the biotechnology industry, are united in a collaborative scheme to achieve a critical mass and to consolidate Europes position as an international leader in the field of Type 2 diabetes and its pathogenesis. With this aim in view, EUGENE2 will group and network experts in functional genomics, genomics, proteomics and bioinformatics to unravel the complex pathogenesis of Type 2 diabetes and the specific role of the skeletal muscle, fat and the liver. In practice, this will involve the dedication and the development of common research infrastructures in human and rodent genomics and bioinformatics combined with cohesive research efforts in proteomics, transcriptional regulation, insulin signalling and action in the target-tissues. A concerted effort in applying functional genomic approaches in target cells, rodents, and humans will generate information necessary to make advances in health care, pharmaceutical development and public health policies.

Web site:

http://www.eugene2.com

Participants:Coordinator Sweden Denmark Finland France Germany Italy Spain Sweden United Kingdom Prof. Ulf Smith, Goteborg University, Department of Internal Medicine, Goteborg tel: +46 31 342 11 04 fax: +46 31 829 138 ulf.smith@medic.gu.se Oluf Pedersen, Steno Diabetes Center, Gentofte Markku Laakso, University of Kuopio, Department of Medicine, Kuopio Emmanuel Van Obberghen, Institut National de la Sante et de la Recherche Medicale, U45, Nice Johan Auwerx, Centre Europeen pour la Recherche en Biologie et Medecine - Groupement d'Interet Economique, Mouse Clinic Institute, Illkirch Hans-Ulrich Haring, Eberhard Karls Universitaet, Medizinische Klinik IV, Tubingen Hans-Georg Joost, German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Pharmacology, Nuthetal Giorgio Sesti, Univ. Studi Magna Graecia di Catanzaro, Dipartimento di Medicina Sperimentale e Clinica "Gaetano Salvatore", Catanzaro Francesco Beguinot, Univ. Napoli Federico II, Dipart. Biol. Pat. Cell. Mol., Fac. Medicine, Naples Fatima Bosch, Universitat Autonoma de Barcelona, Center of Animal Biotechnology and Gene Therapy (CBATEG), Bellaterra Juleen R. Zierath, Karolinska Institutet, Section of Integrative Physiology, Dept. of Surgical Science, Stockholm Nigel Levens, Biovitrum AB, Department of Biology, Stockholm, IND Stephen O'Rahilly, The Chancellor and Masters and Scholars of the University of Cambridge, Department of Clinical Biochemistry, Cambridge

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

EUROPEAN RENAL GENOME PROJECTProposal acronym Contract n Duration (starting date) EuReGene LSHG-CT-2004-005085 5 Years (01.01.05) EC contribution () Instrument Participants 10.500.000 IP 18

Abstract:Diseases of the kidney represent a major cause of morbidity and mortality in Europe. The elderly are disproportionately affected, but renal disease is also a condition that severely affects children. An estimated 4.5 Million Europeans suffer from renal disorders. The death rate in patients with renal failure is 20% annually. This disease burden and its challenge for our societies is the focus of this proposal. Elucidation of the human and other genomes heralds a new era in biomedical research offering unprecedented opportunities to understand disease processes and to identify strategies to improve health. We will embrace these opportunities and implement an interdisciplinary research program, the European Renal Genome Project (EuReGene) that integrates European excellence in research relevant to renal development, pathophysiology and genetics. Our goal is to discover genes responsible for renal development and disease, their proteins and their actions. To achieve this goal, we have established a consortium of leading scientists, clinicians and SME partners that will focus on the development of novel technologies and discovery tools in functional genomics and their application to kidney research. We will rely on comparative genomic studies in many systems that provide utilitarian models ranging from zebrafish, to Xenopus, to mice, to rats. Our studies will be performed at different levels including the gene, the cell, the organ and the organism. Ultimately, identification of disease genes will lead to a better understanding of renal disease processes, to improved diagnosis and to new concepts in therapy. Our program will establish a paradigm for an integrated post-genomic approach to analyze renal disease-related developments that may be transferred to other organ systems or disease entities in the future.

Web site:

http://www.euregene.org

Participants:Coordinator Germany Belgium Denmark Finland France Germany Prof. Thomas E. Willnow, Max-Delbruck-Centrum Molekulare Medizin, Mol. Cardiovascular Res. tel: +49 30 9406 2569 fax: +49 30 9406 3382 willnow@mdc-berlin.de Olivier Devuyst, Universite catholique Louvain, UCL Medical School, Div. Nephrology, Brussels Erik Ilso Christensen, University of Aarhus Anders Nykjaer, ReceptIcon Aps, Aarhus, SME Seppo Juhani Vainio, University of Oulu Andreas Schedl, Institut National de la Sant et de la Recherche Mdicale U470, Nice Corinne Antignac, Inst. Nat. Sant et Recherche Mdicale U574, Necker Hospital, Paris Pierre Verroust, Inst. Nat. Sant et Recherche Mdicale U538, CHU Saint Antoine, Paris Gregor Eichele, Max-Planck Gesellschaft zur Forderung der Wissenschaften, MPI Experimental Endocrinology, Hanover Thomas J. Jentsch, Zentrum fur Molekulare Neurobiologie, Universitat Hamburg Matthias Kretzler, Ludwig-Maximilians-Universitat Munchen - Medizinische Poliklinik, Munchen Giuseppe Remuzzi, Istituto di Ricerche Farmacologiche Mario Negri - Department of Molecular Medicine / Laboratori Negri Bergamo / Istituto di Ricerche Farmacologiche Mario Negri, Milano Jakub Gburek, Wroclaw Medical University Andre Werner Brandli, Swiss Federal Institute of Technology of Zurich Heini Murer, Institute of Physiology, University of Zurich Nicholas Hastie, Medical Research Council - MRC Human Genetics Unit, London Roger Cox, Medical Research Council, MRC Mammalian Genetics Unit, Oxfordshire Rajesh Thakker, Chancellor, Masters and Scholars of the University of Oxford, Nuffield Department of Clinical Medicine, Oxford

Italy Poland Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

NUCLEAR ENVELOPE-LINKED RARE HUMAN DISEASES: FROM MOLECULAR PATHOPHYSIOLOGY TOWARDS CLINICAL APPLICATIONSProposal acronym Contract n Duration (starting date) EURO-Laminopathies LSHM-CT-2005-018690 3 years (01.02.06) EC contribution () Instrument Participants 2.565.000 STREP 11

Abstract:Laminopathies are inherited human disorders, including muscular dystrophy, cardiomyopathy, lipodystrophy, insulinresistance, diabetes, and premature aging, which are linked to mutations in genes encoding nuclear envelope proteins, such as A-type lamins (LMNA) and lamin-binding proteins (EMD, LBR, LAP2). Laminopathies are clinically manifested after birth, progressively develop during childhood or adolescence, and often lead to early death. Efficient therapies have been hampered by the lack of understanding the molecular mechanisms causing the disorders. We will test various disease hypotheses, identify drug targets, and screen drugs for therapeutic interventions. Structural biologists will investigate how disease-causing mutations in A-type lamins or in one of their prominent binding partners LAP2alpha affect atomic structure, interactions, and assembly properties of lamins, which may reduce stress resistance in patient cells. Using patient cells and animal models (mouse, C. elegans) that either lack A-type lamins or LAP2alpha, or express disease variants, we will test how mutations or loss of these proteins affect chromatin organization, gene expression, and differentiation of adult muscle- and adipose stem cells. Differentiation will be studied ex vivo in cell culture, focusing on the molecular functions of A-type lamins and LAP2alpha in differentiation-linked pathways, and in vivo in animal models analyzing muscle regeneration after stress, injury, or aging. Data obtained in these systems as well as chemical compound screening using the zebrafish model system will identify potential drug targets and drugs for testing in animal disease models and for potential therapeutic intervention. Furthermore, we will extend and evaluate clinical trials on the treatment of lipodystrophy-type laminopathy patients with drugs that target the adipocyte differentiation pathway, and develop theranostic tests for the validation of therapies.

Web site:

http://www.projects.mfpl.ac.at/euro-laminopathies

Participants:Coordinator Austria Austria France Germany Israel Italy Dr. Roland Foisner, Department of Medical Biochemistry, Medizinische Universitt Wien, Vienna tel: +43-1-4277-61680 fax: +43-1-4277-9616 roland.foisner@meduniwien.ac.at Brigitte Rohner, Brigitte Rohner punkt, Vienna, SME Gisle Bonne, Inserm U582, Institut de Myologie, G.H. Piti-Salptrire, Institut National de la Sant et de la Recherche Mdicale, Paris Harald Herrmann, Division of Cell Biology A010, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg Yosef Gruenbaum, Department of Genetics, The Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Jerusalem Elisa Gargiullo, R&D Department, DIATHEVA s.r.l., Fano, SME Nadir Mario Maraldi, Laboratory for Cell Biology and Electron Microscopy, Istituti Ortopedici Rizzoli, Bologna Giuseppe Novelli, Department of Biopatologia e Diagnostica per Immagini-Sezione di Genetica, Universita' degli Studi di Roma Tor Vergata, Rome Ueli Aebi, M.E. Mueller Institute for Structural Biology (MSB), Biozentrum, University of Basel Paul, Goldsmith, DanioLabs Discovery and Development, DanioLabs Limited, Cambridge, SME Christopher John Hutchison, Integrative Cell Biology Laboratory, School of Biological and Biomedical Sciences, University of Durham

Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

EUROPEAN NETWORK TO PROMOTE RESEARCH INTO UNCOMMON CANCERS IN ADULTS AND CHILDREN: PATHOLOGY, BIOLOGY AND GENETICS OF BONE TUMOURSProposal acronym Contract n Duration (starting date) EuroBoNet LSHC-CT-2006-018814 5 years (01.02.06) EC contribution () Instrument Participants 13.218.960 NoE 24

Abstract:Leading trans European research groups will integrate expertise to increase and disseminate knowledge of primary bone tumours at the molecular level for development of new tools for patient care and cure. Primary bone tumours are rare, accounting ~0.2% of the cancer burden. Children and young adolescents are frequently affected. Their aggressiveness has major impact on morbidity and mortality. Though progress has been made in pathological and genetic typing, the aetiology is largely unknown. Advances in therapeutic approaches increased survival. Significant numbers of patients (~40%) still die from disease. Within a network of experts an exchange of material, knowledge and technology is achieved to obtain statistical significant datasets, otherwise not achievable due to the rareness and the large number of sub entities (the 2002 WHO classification recognises 31 different bone tumours. A joint programme will contribute in obtaining molecular portraits of tumours. We focus on the molecular level, which is expedient since the availability of the wealth of information from the Human Genome Project. Several bone tumours occur within a hereditary syndrome, underpinning importance of combining a tumour and clinical genetic approach. Most tumours yield a complex and as yet not tumourspecific genetic make-up. Some specific genetic events are reported, but this knowledge is not transcribed into comprehensive understanding, nor does it give an anchoring point for designing tumour specific therapy. The WHO has proclaimed (endorsed by EC member countries) the Bone and Joint Decade, to improve the health-related quality of life for patients with skeletal disorders. It aims to advance understanding through research improving prevention and treatment. This is optimal done in a multi-institutional network of expertise. Patients usually do not present themselves at centres, which necessitates spreading of knowledge from the network into the community via a joint training program.

Web site:

http://www.eurobonet.org

Participants:Coordinator Netherlands Belgium Denmark Finland Germany Prof. Pancras C.W. Hogendoorn, Leiden University Medical Center, Depart. Pathology, Leiden tel: +31 71 52 66 639 fax: +31 71 52 48 158 p.c.w.hogendoorn@lumc.nl Ramses Forsyth, N. Goormaghtigh Institute of Pathology, Ghent Wim Wuyts, Universiteit Antwerpen, Department of Medical Genetics, Antwerp Raf Sciot, Katholieke Universiteit Leuven, University Hospital, Dept. of Pathology, Leuven Sren Daugaard, Rigshospitalet, Department of Pathology, Copenhagen

Hungary Italy Netherlands Norway Spain Sweden Switzerland United Kingdom

Sakari Knuutila, Helsinki University Central Hospital, Laboratory of Cytomolecular Genetics, Division of Pathology, Helsinki Christopher Poremba, Heinrich-Heine-University Dsseldorf, Institute of Pathology, Dsseldorf Thomas Aigner, Friedrich-Alexander-University Erlangen-Nrnberg, Osteoarticular and Arthritis Research, Department of Pathology, Erlangen Horst Brger, Westflische Wilhelmsuniversitt Mnster, Gerhard-Domagk-Institut fur Pathologie, Munster Miklos Szendroi, Semmelweis University Budapest, Orthopaedics Department, Budapest Piero Picci, Istituti Ortopedici Rizzoli, Bologna Angelo Paolo Dei Tos, Treviso Hospital, Department of Pathology, Treviso Jos Joore, Pepscan Systems B.V., Lelystad, SME Jan Schouten, MRC Holland bv, Amsterdam, SME Pieter Hendrik Jan Riegman, Erasmus Medical Center Rotterdam Ola Myklebost, University of Oslo, Norwegian Radium Hospital, Institute for Cancer Research, Dept. of Tumour Biology and Institute for Molecular Bioscience, Oslo Enrique de Alava, Laboratory of Molecular Pathology, University of Salamanca Fredrik Mertens, Lund University, Depart. Clinical Genetics, Institute of Laboratory Medicine, Lund Pierre Mainil-Varlet, University Bern, Institute of Pathology, Osteoarticular Research Group, Bern Rob Grimer, Royal Orthopaedic Hospital, Department of Musculoskeletal Pathology, Birmingham Nicholas Anthony Athanasou, University of Oxford, Nuffield Depart. Orthopaedic Surgery, Oxford

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

ADVANCES IN HEARING SCIENCE: FROM FUNCTIONAL GENOMICS TO THERAPIESProposal acronym Contract n Duration (starting date) EuroHear LSHG-CT-2004-512063 5 Years (01.12.04) EC contribution () Instrument Participants 12.500.000 IP 26

Abstract:EuroHear has two closely inter-related objectives. These are (1) to provide fundamental knowledge about the development and function of the inner ear, and (2) to identify the molecular defects underlying hereditary hearing impairments (HI), including presbycusis, one of the most frequent forms of HI. Achieving these objectives will facilitate the development of therapies for alleviating HI. In order to address the above issues, the EuroHear project is organised into 4 components: 1- The identification of genes underlying sensorineural HI in humans and mice. 2- The analysis of the molecular and cellular mechanisms underlying the development and function of: the hair bundle; the ribbon synapses of the hair cell and outer hair cell electromotility; the ion channels, ion transporters and gap junction channels that contribute to the potassium homeostasis. 3- The standardisation, implementation and development of technologies. 4The development of new tools for preventing and curing HI. Currently, we identify a multidisciplinary approach as the sina qua non condition for further progress in understanding the inner ear. The EuroHear consortium comprises a group of laboratories that are world experts in a variety of hearing research fields. EuroHear is a continuation and extension of a previous European consortium that has successively tackled early-onset, Mendelian forms of deafness and hearing loss. The success of this European consortium, which has identified half of the 37 known genes for isolated forms of HI in humans, has been due in large part to intense collaboration between human and mouse geneticists. Expected contributions of EuroHear include a standardisation of investigative protocols, the provision of access to large-scale platforms for genetics and genomic analysis, the development and diffusion of physiological and biophysical techniques of relevance for functional investigations of the inner ear, the creation of a variety of mouse.

Web site:

http://www.eurohear.org

Participants:Coordinator France Belgium Finland France Prof. Christine Petit, Institut de la Sante et de la Recherche Medicale, U587, Inst. Pasteur, Paris tel: +33 1 45 17 26 60 fax: +33 1 45 17 26 78 cpetit@pasteur.fr Guy Van Camp, Universiteit Antwerpen, Department of Medical Genetics, Antwerpen Ulla, Pirvola, University of Helsinki, lnstitute of Biotechnology, Helsingin Yliopisto Mark Lathrop, Consortium National de Recherche en Genomique, Centre Nat. Genotypage, Evry Jacques, Prost, lnstitut Curie, Division de Recherche, Paris Jorg Hager, IntegraGen SA, Evry, SME Marc Poirot, Affichem, Toulouse, SME Jonathan Dando, Inserm Transfert SA, European Project Management Department, Paris Dominik Oliver, Universitaet klinikum Freiburg, Physiologisches Institut II, Freiburg Jonathon Howard, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden Thomas J. Jentsch, Universitaetsklinikum, Zentrum Molekulare Neurobiologie (ZMNH), Hamburg Christian Kubisch, Universitaet klinikum Bonn, lnstitute of Human Genetics, Bonn Tobias Moser, Bereich Humanmedizin Georg August, Dept. of Otorhinolaryngology, Goettingen Klaus Willecke, Institute of Genetics University of Bonn, Institute of Genetics, University of Bonn E. Sylvester Vizi, Institute of Experimental Medicine, Hungarian Academy of Sciences, Department of Pharmacology, Budapest Karen Avraham, Tel Aviv University, Dept. of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv Fabio Mammano, Istituto Veneto di Medicina Molecolare (VIMM), Padova Cor W.R.J. Cremers, Stichting Katholieke Universiteit, University Medical Centre Nijmegen, Otorhinolaryngology, UMCN, Catholic University Nijmegen, Nijmegen Felipe Moreno, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal, Unidad de Genetica Molecular, Hospital Ramon y Cajal, Madrid Mats Ulfendahl, Karolinska Institutet, Dept of Clinical Neuroscience, Stockholm Christian, Vieider, Acreo AB, MicroTechnology Department, Kista / Stockholm, SME Hammadi Ayadi, Faculty Medicine Univ. Sfax, Human Molecular Genetics Laboratory, Sfax Jonathan Ashmore, University College London, Depart. of Physiology, University College London Steve Brown, Medical Research Council, MRC Mammalian Genetics Unit, Oxfordshire Guy Peel Richardson, University of Sussex, School of Life Sciences, Falmer, Brighton Karen Steel, Genome Research Limited, The Wellcome Trust Sanger Institute, Cambridge

Germany

Hungary Israel Italy Netherlands Spain Sweden Tunisia United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

EUROPEAN MANTLE CELL LYMPHOMA NETWORK: TRANSLATIONAL DETERMINATION OF MOLECULAR PROGNOSTIC FACTORS AND PHARMACOGENOMICS IN A EUROPEAN INTERDISCIPLINARY COLLABORATIONProposal acronym Contract n Duration (starting date) EUROPEAN MCL NETWORK LSHC-CT-2004-503351 3 years (01.07.04) EC contribution () Instrument Participants 2.493.900 STREP 17

Abstract:Mantle cell lymphoma (MCL) is a distinct, clinically very aggressive subentity of malignant lymphoma with a median survival of 3 years. However, a small subset of patients represents long-term survivors. So far, the discriminative power of different prognostic parameters has been limited and did not allow the reliable identification of the individual patient's risk profile. Thus, a better understanding of the underlying molecular mechanisms is eagerly warranted. In the last few years, European-wide MCL networks of clinicians (European MCL Intergroup Working Party), pathologists (European MCL Pathology Panel) and basic researchers (European MCL Research Network) have been established to investigate the clinical as well as molecular aspects of malignant transformation and progression in MCL. Especially, strict diagnostic histomorphological criteria have been defined; in a prospective randomized study, an intensive consolidation with high dose radiochemotherapy and subsequent autologous stem cell transplantation resulted in superior progression-free and overall survival rates; and most interestingly, proliferation indices have been identified as the most important prognostic factors in MCL superior to clinical parameters (IPI). Based on these extensive prerequisites and the recent development of innovative molecular techniques (matrix CGH, RNA array chips, RQ-PCR, proteomics), we propose a global approach to investigate innovative treatment options of MCL and evaluate new predictive (pharmacogenomics, minimal residual disease) and prognostic molecular markers (genomic alterations, RNA/proteome profiles) in such controlled studies. This translational approach of the European MCL Network will not only lead to more individualized therapeutic strategies based on a molecular risk profile but will also finally elucidate the way to future molecular targeted treatment options in a subtype of malignant lymphoma with an otherwise dismal clinical outcome.

Web site:

http://www.lymphome.de/en/Projects/MCL

Participants:Coordinator Germany Czeck Republic Denmark France Dr. Martin Dreyling & Prof. Wolfgang Hiddemann, Ludwig-Maximilians-Universitt Muenchen & Univ. Munich - Department of Internal Medicine III, Munich tel: +49 897 095 2550 fax: +49 897 095 5550 martin.dreyling@med.uni-muenchen.de Marek Trneny, Kooperativni lymfomova skupina (Czeck Lymphoma Study Group), Prague Niels Andersen, Rigshospitalet, University Hospital Copenhagen Gilles Salles, Evelyne Calle-Bouchu & Catherine Thieblemont, Universite Claude Bernard Lyon-1 & Hematology Laboratory of Centre Hospitalier Lyon-Sud, Pierre-Bnite / Lyon Elisabeth Macintyre, UFR Necker-Enfants Malades, Universite Paris V Vincent Ribrag, Institut Gustave Roussy, Villejuif Christiane Pott, Reiner Siebert & Reza Parwaresch, Christian-Albrechts-Universitt zu Kiel, Tumor Genetics Group at the Institute of Human Genetics of the University Hospital of Kiel & Institute of Hematopathology and Lymph Node Registry of Kiel Thomas Meitinger, GSF National Research Institute for Environment and Health, Neuhenberg German Ott & Andreas Rosenwald, Institute of Pathology, University of Wrzburg Brigitte Schlegelberger, Institute of Cell and Molecular Pathology, Medical School of Hannover Stephan Stilgenbauer, Medizinische Fakultt, Universitt Ulm Philip Kluin, University Hospital Groningen Jacobus Johannes Maria van Dongen, Erasmus University Medical Center Rotterdam Johannes H.J.M. van Krieken, University Medical Centre Nijmegen, Stichting Katholieke Universiteit Jan Walewski, Polish Lymphoma Research Group, Warzawa Jose Angel Martinez-Climent, Hospital Clinico, Center for Applied Medical Research, Pamplona Elias Campo, Hospital Clinic Provincial de Barcelona

Germany

Netherlands

Poland Spain

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer Sector

MOLECULAR CONTROL OF ERYTHROPOIESISProposal acronym Contract n Duration (starting date) EURYTHRON MRTN-CT-2004-005499 4 years (01.11.04) EC contribution () Instrument Participants 2.875.996 Marie-Curie RTN 7

Abstract:Red blood cells (RBCs) mediate oxygen transport throughout the body, a function that is essential for life. RBCs are continuously produced via a process called erythropoiesis. Anemias (insufficient numbers of functional RBCs), caused by failure of erythropoiesis, are a major cause of disease in the EC. The hereditary anemias constitute the most common human genetic disorders, with no effective cure yet. We propose an RTN "Molecular Control of Erythropoiesis" which will foster a multidisciplinary approach to clarify the important molecular mechanisms in normal and pathological erythropoiesis, with a view to develop novel therapies to cure the anemias. The RTN will generate a comprehensive molecular description of mechanisms governing erythropoiesis, from specification of hematopoietic stem cells in embryogenesis to terminal differentiation and post-mitotic maturation of red blood cels. For this, the RTN will use and further develop a large number of state of the art approaches in stem cell- and erythroid cell biology, including in vitro expansion, biochemistry of receptor / signal transducer complexes and transcription factors, and epigenetics. This mechanistic knowledge obtained within the RTN will be instrumental to devise intervention strategies for anemias and other erythroid disorders (e.g. dysplasias and leukemias). The RTN aims to (a) provide an international training platform for young scientists, (b) integrate European top-level genomics-oriented research in the area of hematopoietic disorders, and (c) serve as a link to industrial partners, with a view to enhance the career perspectives of young scientists in the European Research Area.

Web site:

http://www.eurythron.org

Participants:Coordinator Netherlands Dr. Sjaak Philipsen (Cell Biology), Erasmus Universitair Medisch Centrum, Rotterdam also: Elaine Dzierzak & Frank Grosveld (Cell Biology) & Marieke von Lindern (Hematology), Erasmus MC, Rotterdam tel: +31-10-4088282 fax: +31-10-4089468 j.philipsen@erasmusmc.nl Hartmut Beug, Institute of Molecular Pathology, Vienna Paul-Henri Romeo, Patrick Mayeux & Claire Francastel, Institut Cochin, Haematology Department, Paris Anna Rita Migliacioo, Istituto Superiore Sanit, Rome Gerald de Haan, Depart. Stem Cell Biology, Fac. Medical sciences, University of Groningen Maria Carmo Fonseca, Laboratory of cell biology, Institute of Molecular Medicine, Lisbon Doug Higgs,Tariq Enver & Roger Patient, Weatherall Institute of Molecular Medicine, Oxford

Austria France Italy Netherlands Portugal United Kingdom

Commission: Directorate General for Research - Human ressources and Mobility Directorate - Marie Curie Actions

EUROPEAN TRANSCRIPTOME, REGULOME AND CELLULAR COMMITMENT CONSORTIUMProposal acronym Contract n Duration (starting date) EuTRACC LSHG-CT-2006-037445 4 years (01.01.07) EC contribution () Instrument Participants 9.600.000 IP 18

Abstract:The EuTRACC consortium proposes to determine the regulation of the genome by mapping the regulatory pathways and networks of transcription factors that control cellular functions. EuTRACC will be part of and work in close collaboration with the International Regulome Consortium (IRC), an worldwide network that will address the regulation of genome function at a higher level by mapping the genetic regulatory nodes and networks that control the activity of embryonic stem cells and the process of differentiation to specific cell types. This Integrated Project will focus on mapping the genetic circuitry that controls the formation of neural tissues and the blood system. The project will utilize genetics, proteomics and genomics tools in the mouse, zebrafish and xenopus model organisms.

Web site:

not yet

Participants:Coordinator Netherlands Austria Canada France Germany Prof. Frank Grosveld, Department of Cell Biology, Erasmus University Medical Center, Rotterdam tel: +31-10-4087593 fax: +31-10-4089468 f.grosveld@erasmusmc.nl Meinrad Busslinger, Research Institute of Molecular Pathology, Research Institute of Molecular Pathology GmbH, Vienna Michael Rudnicki, International Regulome Consortium, Ottawa Health Research Institute, Ottawa Laszlo Tora, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre Europeen pour Recherche en Biologie et Medecine, Groupement d'Interet Economique, Illkirch Michael Meisterernst, Institute of Molecular Immunology, Forschungszentrum fur Umwelt und Gesundheit, Munich, Neuherberg Ferenc Muller, Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe GmbH, Karlsruhe Martin Vingron, Department of Computational Biology, Max Planck Society, represented by the Max Planck Institute for Molecular Genetics, Berlin Thomas Werner, Genomatix Software GmbH, Munich, SME Francis A. Stewart, Biotec, Genomics, Technische Universitat Dresden, Dresden Roberto Di Lauro, CEINGE Biotecnologie Avanzate S.C.a r.l., Naples Hermanus Theodorus Marc Timmers, Department of Physiological Chemistry - Division of Biomedical Genetics, University Medical Centre Utrecht, Utrecht Boris Lenhard, Bergen Center for Computational Science, Computational Biology Unit, Universitetet i Bergen, Bergen Yves-Alain Barde, Division of Pharmacology/Neurobiology, Biozentrum, University of Basel Timothy Allsopp, Stem Cell Sciences UK Ltd, Edinburgh, SME William Skarnes, Team 107, Wellcome Trust Sanger Institute, Hinxton, Cambridge Roger Patient, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Medical Research Council, Headington, Oxford, London Jim Smith, Wellcome Trust, Cancer Research UK, Gurdon Institute, The Chancellor, Master & Scholars of the University of Cambridge Constanze Bonifer, Division of Experimental Haematology, School of Medicine, IMMECR, University of Leeds, Leeds

Italy Netherlands Norway Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

FUNCTIONAL GENOMICS OF THE RETINA IN HEALTH AND DISEASEProposal acronym Contract n Duration (starting date) EVI-GENORET LSHG-CT-2005-512036 4 Years (01.04.05) EC contribution () Instrument Participants 10.000.000 IP 24

Abstract:The retina is a highly complex biological system that accommodates both numerous tissue-specific and ubiquitously expressed developmental and pathologic pathways. The number of genes identified in Inherited Retinal Degenerations (IRD) has steadily increased. The commonest cause of blindness, (12.5 Million affected in Europe) Age-RelatedMacular-Degeneration (ARMD), is likely to depend on both mostly unknown genetic and modifying factors. Preventing blindness from IRD and ARMD requires the understanding of the genetic and cellular interactions controlling retinal development, maintenance and function. In EVI-GENORET 24 academic and industrial partners form five interacting components (phenotyping, development, genetics, therapy and functional genomics) to establish working platforms, share tools and knowledge within and outside the academic community (dissemination through patient organisations and transfer to industrial partners). This IP, spanning from the biology of seeing to the fight against retinal blindness, will implement an accurate clinical and molecular classification of disease, identify novel retinal genes and pathways and define the context dependent functions of these genes in normal and degenerating tissue. The goal of the EVIGENORET consortium is to devise plans for the development of broad scale approaches to integrating biological sciences over the micro- to macro-scales. Therefore, we will employ transcriptome, proteomics, protein-interactome analyses, functional cellular and biochemical assays, bioinformatics and model organisms to analyse patterns of gene expression and gene function in retinal development, normal function and degeneration. The unique knowledge base on molecular networks thus generated will facilitate identification and validation of novel therapeutic targets, of broad interest. Developing stem cell culture methods and new approaches to gene and drug delivery mechanisms should provide novel tools for therapy after testing in this privileged organ. An effective project management is ensured by the creation of the European Vision Institute (EVI), a EEIG devoted to fostering European Vision Research.

Web site:

http://www.evi-genoret.org

Participants:Coordinator Belgium France Prof. Jose Alain Sahel, European Vision Institute EEIG, Brussels tel: +32 2 548 02 25 fax: +32 2 548 02 25 info@evi-genoret.org Jose Alain Sahel, Institut National de la Sante et de la Recherche Medicale, Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Paris Pascal Dolle, Centre Europeen pour la Recherche en Biologie et Medecine, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch Kader Thiam, Genoway, Lyon, SME Laure Benhamou, Inserm Transfert SA, Paris Eberhart Zrenner, Eberhard-Karls-Universitaet Tuebingen, University Eye Hospital, Tuebingen Marius Ueffing, GSF-Forschungszentrum fur Umwelt und Gesundheit GmbH, Institute of Human Genetics, Neuherberg Andreas Gal, University Hospital Hamburg-Eppendorf, Institute of Human Genetics, Hamburg Frank G Holz, University of Heidelberg, Department of Ophtalmology, Heidelberg Frank Muller, Research Centre Juelich, Institute for Biological Information Processing, Juelich Nicolas Anagnou, National and Kapodistrian University of Athens, School of Medicine, Laboratory of Biology, Athens Peter Humphries, Trinity College Dublin (TCD), Dept. Genetics, , Ocular Genetics Unit, Dublin Gearoid Tuohy, Genable Technologies Limited, TCD, Dublin, SME Valeria Marigo, Fondazione Telethon, Institute of Genetics and Medicine, Naples Angelo Luigi Vescovi, Univ. Milano Bicocca, Dipartimento di Biotecnologie e Bioscienze, Milan Ronald Roepman, University Medical Centre Nijmegen / University of Nijmegen, Division Molecular Genetics, Dept. of Human Genetics, Nijmegen Rui Bernardes, AIBILI - Associacio para Investigacio Biomedica e Inovacio em Luz e Imagem, CNTM- Centro de Novas Tecnologias para a Medicina, Coimbra, SME Carmen Ayuso, Fundacion Jimenez Diaz UTE, Department od Medical Genetics, Madrid Theo van Veen, Lunds Universitet, Department of Ophtalmology, Wallenberg Retina Center, Lund Christian Grimm, University of Zurich, University Eye Hospital, Lab of Retinal Cell Biology, Zurich Christina Fasser, Retina International, Zurich Shomi Bhattacharya, University College London, Inst. Ophtalmology, Dept. Mol. Genetics, London Veronica VanHeynigen, Medical Research Council, MRC Human Genetics Unit, Edinburgh Usha Chakravarthy, The Queen's University of Belfast, Ophtalmology and Vision Science, Belfast

Germany

Greece Ireland Italy Netherlands Portugal Spain Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

FUNCTIONAL GENOMICS IN ENGINEERED ES CELLSProposal acronym Contract n Duration (starting date) FunGenES LSHG-CT-2003-503494 3 years (01.03.04) EC contribution () Instrument Participants 8.500.000 IP 18

Abstract:The complete sequence of a mammalian genome defines the total information content. The next major challenge is to understand how the information is used in subsets during development - subsets that define multipotential states (stem cells); subsets that define differentiated states; and how the transitions between these states are made (lineage commitment). The research partnership, FunGenES, will address this challenge. FunGenES will map, using both expression profiling and high throughput functional screens, the subsets used in pluripotent, lineage committed and selected differentiated cell types to make an atlas of mammalian genome utilization in early development. The remarkable properties of mouse ES cells are key to the proposal. These cells are pluripotent, can be differentiated through the three major developmental pathways; ecto- endo- and mesoderm, to many differentiated cell types, and can be engineered. Manipulation of mouse ES cells also presents paradigms for the development of cell therapies. To accomplish this next, major, milestone in human biology, we have assembled a team of leading academic and commercial experts in the major pathways of ES cell differentiation, anchored by common services provided by world leaders in three technology areas. These areas are - BAC transgene engineering (for efficient production of lineage reporter and selectable lines), RNAi (esiRNA; for high throughput functional screens) and database management of expression profiling. Because these resources are centralized, and methodologies are unified for all of FunGenES, the substantial aim to generate a functional and expression atlas database will be accomplished efficiently. The atlas is the first goal. It will provide hypotheses for testing with advanced functional tools. By understanding how mammalian genomic information is selectively used in development, we will acquire an essential key to understanding ourselves, and our health.

Web site:

http://www.fungenes.org

Participants:Coordinator Germany France Prof. Jrgen Hescheler, Universitt Kln tel: +49 221 478 737 3 fax: +49 221 478 383 34 j.hescheler@uni-koeln.de Laurent Pradier, Aventis Drug Innovation & Approval, Vitry-sur-Seine, IND Pierre Savatier, Institut National de la Sant et de la Recherche Mdicale, Lyon Christian Dani, Centre National de la Recherche Scientifique, Nice Annette Ringwald, ARTTIC SA, Paris

Germany

Antonis Hatzopoulos, GSF-National Research Centre for Environment and Health, Neuherberg Matthias Austen, DeveloGen Aktiengesellschaft fr entwicklungsbiologische Forschung, Goettingen, SME Michael Bader, Max-Delbrck-Center for Molecular Medicine, Berlin Frank Buchholz, Max-Planck-Society, Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden Heinz Himmelbauer, Max-Planck-Institute of Molecular Genetics, Berlin Francis Stewart, Technical Universitt Dresden Anna M. Wobus, IPK Gatersleben, Institute of Plant Genetics and Crop Plant Research Androniki Kretsovali, Foundation for Research & Technology Hellas - Institute of Molecular Biology and Biotechnology, Heraklion Angelo Luigi Vescovi, Fondazione Centro San Raffaele del Monte Tabor, Institute for Stem Cell Research, Milan Domingos Henrique, Instituto de Medicina Molecular, Lisbon Lesley Forrester, University of Edinburgh Tim Allsopp, Stem Cell Sciences Ltd, West Lothian, SME Melanie Welham, The University of Bath

Greece Italy Portugal United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

HEART FAILURE AND REPAIRProposal acronym Contract n Duration (starting date) HeartRepair LSHM-CT-2005-018630 4 years (01.01.06) EC contribution () Instrument Participants 11.400.000 STREP 26

Abstract:HeartRepair uses the lessons of the embryo to answer the crucial developmental questions regarding heart muscle cell differentiation and develop techniques aimed at harnessing stem cells and or recruiting non-damaged myocardial cells from the infarcted heart to facilitate cardiac repair. Myocardial infarction is the leading cause of congestive heart failure mainly caused by excessive smoking and bad dietary habits. However, the cause of the subsequent heart failure is simple, massive cardiomyocyte necrosis which fatally perturbs heart function. However, an effective therapeutic approach is simple: replacement of damaged myocardium with viable cardiomyocytes. Recent advances in the field of stem cell replacement therapies, specifically cardiomyocyte regeneration, gains grace as a realistic alternative for congestive heart repair. Major publications revolve around transplantation trials carried out using either embryonic stem cells or bone marrow derived stem cells. However, Field serious questions the current scientific approach to this research and more importantly if, using current techniques and knowledge, such a goal can realistically ever be reached. Realization of this aim will only be achieved by understanding the underlying principles of cardiac muscle cell formation; the mission statement of HeartRepair HeartRepair addresses four R&D themes: 1. Genes for heart repair and plasticity, integrating clinical knowledge based genome sequencing to identify genes involved in heart development 2. Diversification of cardiac progenitor cells, examining the genetics of cardiac muscle cell formation by exploring the process of cardiomyogenesis and subsequent differentiation 3. Cell interaction and cardiac reprogramming, exploring the details and signals necessary to facilitate and redirect the cardiac fibroblast cell lineage for repair recruitment 4. Cardiac rejuvenation, to develop techniques to facilitate and speed repair of damaged, not yet necrotic, myocardium.

Web site:

http://www.heartrepair.eu

Participants:Coordinator Netherlands France Germany Prof. Antoon F. Moorman, Depart Anatomy & Embryology, Academic Medical Centre, Amsterdam tel: +31 205664928 fax: +31 206976177 a.f.moorman@amc.uva.nl Robert George Kelly, Laboratoire de Gntique et Physiologie du Dveloppement, Institut de Biologie du Dveloppement de Marseille, Marseille Margaret Elizabeth Buckingham, Gntique Mol. du Dveloppement, Institut Pasteur, Paris Andreas Kispert, Institut fuer Molekularbiologie, Medizinische Hochschule Hannover, Hannover Stefanie Dimmeler, Molecular Cardiology, University of Frankfurt, Frankfurt Silke Sperling, Cardiovascular Genetics, Max Planck Society, Max Planck Institute for Molecular Genetics, Berlin Ulrike Bauer, Competenz Network, Kompetenz Angeborene Herzfehler, Berlin Marina Campione, Institute of Neurosciences, National Research Council, Padova Giulio Cossu, Stem Cell Research Institute, DIBIT, Istituto Scientifico San Raffaele, Fondazione Centro San Raffaele del Monte Tabor, Milan Nadia Rosenthal, Mouse Biology Programme, EMBL, Monterotondo Scalo Stefano Schiaffino, Dipart. Scienze Biomediche Sperimentali, Univ. degli Studi di Padova, Padova Christine Mummery, Hurbrecht Laboratory, Utrecht Maurice van den Hoff, Department of Anatomy & Embryology, Faculty of Medicine, Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam Peter Abraham Christiaan 't Hoen, Human & Clinical Genetics, Leiden Univ. Med. Center, Leiden Ingrid Kamerling, Research Department, Netherlands Heart Foundation, The Hague Barbara JM Mulder, Depart. Cardiology, Academic Medical Center, AMC Clinical, Amsterdam Vincent M. Christoffels, Department of Anatomy & Embryology, Faculty of Medicine, Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam Diego Franco, Department of Experimental Biology, Faculty of Health and Experimental Sciences, Cardiovascular Development Group, Universidad de Jaen, Jaen Ramon Munoz Chapuli, Faculty of Science, Department of Animal Biology, University of Malaga Jos Mara Prez-Pomares, Cardiovascular Development and Angiogenesis, Depart. Biologa Animal, Facultad de Ciencias, University of Mlaga & National Center of Biotechnology, Mlaga Petter Bjorquist, Cellartis AB, Cellartis AB, Gothenburg, SME Andreas Zisch, Dept. of Obstetrics, University Hospital Zurich, University of Zurich Nigel Andrew Brown, Anatomy & Developmental Biology, Saint George's Hospital Medical School, University of London John Burn, Inst. Human Genetics, Internat. Centre for Life, University of Newcastle upon Tyne Judith Goodship, Institute of Human Genetics, University of Newcastle upon Tyne Wolfgang Huber, European Bioinformatics Institute, EMBL, Cambridge

Italy

Netherlands

Spain

Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

GENE NETWORKS IN CORTICAL INTERNEURON DEVELOPMENT: MODELING INTERNEURON FUNCTION IN HEALTH AND DISEASEProposal acronym Contract n Duration (starting date) INTERDEVO LSHM-CT-2004-005139 3 Years (01.01.05) EC contribution () Instrument Participants 2.000.000 STREP 8

Abstract:The neural assembly underlying the formation of functional networks in the cerebral cortex constitutes one of the most complex neuronal systems in the brain. Much of this complexity arises during development through the interaction of two distinct neuronal types, the glutamatergic projection neurons and g-aminobutyric containing (GABAergic) interneurons. Recently, interneuron dysfunction has been associated with severe neurological and psychiatric disorders (e.g. epilepsy, schizophrenia and bipolar disorder). In order to achieve true progress in the understanding of cortical development and of neurological diseases associated with cortical interneuron dysfunction, a complete account of the development of its neuronal constituents is essential. In that sense, despite the detailed picture that is emerging about the development of cortical projection neurons, the mechanisms underlying the development of interneurons in the cerebral cortex have remained poorly defined. The general goal of the network is to obtain a comprehensive definition of the cellular and molecular mechanisms controlling the development of cortical interneurons. To reach this aim, we will take a multidisciplinary approach by combining novel bioinformatic and genomics applications, cutting-edge imaging techniques, and conventional cellular, molecular and electrophysiological methodologies. In addition, we will develop new genetic tools to engineer developmental models of cortical disorders involving interneuron deficiency. Thus, successful execution of the project will result in: i) New knowledge of the mechanisms underlying the specification, migration and terminal differentiation of cortical interneurons, and ii) Generation of new developmental models of cortical disorders resulting from interneuron deficiency.

Web site:

http://in.umh.es/interdevo

Participants:Coordinator Spain France Greece Italy Spain Dr. Oscar Marin, Consejo Superior de Investigaciones Cientificas, Instituto de Neurociencias, Unidad de Neurobiologia del Desarrollo, San Joan d'Alacant tel: +34 91 585 5000 fax: +34 91 411 3077 presidente@csic.es Alessandra Pierani, Centre national de la recherche scientifique, Department of Biology Regionalisation Nerveuse, Ecole Normale Superieure, Paris Domna Karagogeos, Foundation for Research and Technology - Hellas, Institute of Molecular Biology and Biotechnology, Heraklion Michele Studer, Fondazione Telethon, Telethon Institute of Genetics and Medicine, Naples Tamara, Maes, Oryzon Genomics Sa, Oryzon Genomics, Barcelona, SME Oscar Marin, Universidad Miguel Hernandez, Instituto de Neurociencias, Unidad de Neurobiologia del Desarrollo, San Joan d'Alacant Liset Menendez de la Prida, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal, Dept Neurobiologia-Investigacion, Laboratory of Neuronal Circuits, Madrid Vassilis Pachnis & Peter Somogyi, Medical Research Council, MRC - National Institute for Medical Research (NIMR), Division of Molecular Neurobiology, London

United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

GENOME-WIDE DISCOVERY AND FUNCTIONAL ANALYSIS OF NOVEL GENES IN LYMPHANGIOGENESISProposal acronym Contract n Duration (starting date) LYMPHANGIOGENOMICS LSHG-CT-2003-503573 5 years (01.05.04) EC contribution () Instrument Participants 9.000.000 IP 13

Abstract:The lymphatic vasculature is essential for the maintenance of fluid balance in the body, for immune defence and for the uptake of dietary fat. Absent or damaged lymphatic vessels can lead to lymphedema, a chronic and disfiguring swelling of the extremities, sometimes necessitating amputation of the affected limb. In addition, lymphatic vessels promote metastatic spread of cancer cells to distant organs - a leading cause of death in patients with cancer, and a major obstacle in the design of effective therapies. The lymphatic vessels were identified hundreds of years ago, yet very limited understanding exists of their development, function and molecular mechanisms underlying their disease processes. The aim of this proposal is to discover novel genes important for lymphatic vascular versus blood vascular development and function and to study the functional role and therapeutic potential of their gene products in lymphangiogenesis using stateof-the art technologies. The methods we plan to use include large-scale knockout and knock-down of the mouse genome, the embryonic stem (ES) technology, knock-down of the zebra fish genes by morpholino-antisense and positional cloning of disease susceptibility genes involved in lymphangiogenesis. These studies will provide fundamental new understanding of the molecular and cellular basis of lymphangiogenesis and therefore enable scientists to develop therapies to suppress the growth of lymphatic vessels (eg. for cancer, inflammatory diseases) or to stimulate their growth (eg. for tissue ischemia, lymphedema). The proposed Integrated Project puts forward ambitious, competitive research objectives addressing biological processes of high medical importance using a multidisciplinary analysis and validation approach. The participants including three European SMEs will also work according to an agreed exploitation plan for the selected targets.

Web site:

http://www.lymphomic.org

Participants:Coordinator Finland Austria Belgium Finland France Germany Italy Sweden Kari Alitalo, University of Helsinki tel: +35 8 919 125 511 fax: +35 8 919 125 510 Kari.alitalo@helsinki.fi Dontscho Kerjaschki, Medical University of Vienn Miikka Vikkula, Christian de Duve Institute of Cellular Pathology, Brussels Peter Carmeliet, Flanders Interuniversity Institute for Biotechnology VIB, Leuven Seppo Yla-Herttuala, University of Kuopio Jyrki Ingman, Lymphatix Oy (Lymphatix Ltd), Helsinki, SME Anne Eichmann, Institut national de la sant et de la recherche mdicale, Paris Hellmut Augustin, KTB Tumorforschungsgesellschaft mbH, Freiburg Elisabetta Dejana, Fondazione Italiana per la Ricerca sul Cancro, Milano Christer Betsholtz, Goteborg University Lena Claesson-Welsh, Uppsala University Mats Hellstrm, AngioGenetics Sweden AB, Goteborg, SME Gerhard Christofori, University of Basel

Switzerland

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

MIGRATING CANCER STEM CELLS IN BREAST AND COLON CANCERProposal acronym Contract n Duration (starting date) MCSCs LSHC-CT-2006-037603 3 years (01.11.06) EC contribution () Instrument Participants 2.150.068 STREP 5

Abstract:Although cancer stem cells (CSC) have received much attention in the recent scientific literature, they are still defined by their self-renewal capability, a feature that on its own does not encompass other essential characteristics of these cells, e.g. their capacity to detach and migrate away from the primary site and invade distal organs. This operational definition of the migrating cancer stem cell (MCSC) is integral to another feature of neoplastic diseases, namely tumour heterogeneity. CSCs give rise to differentiated cells by asymmetric division thus providing a reservoir of multipotent descendants together with proliferating but progressively differentiating cells. Recent experimental evidences point out that cancer stem cells are key factors not only in local invasion and distant metastasis but also in the development of drug resistance, thus representing the target for novel strategies towards tailor-made cancer therapies. The increasing knowledge of the structure and regulation of the mouse and human genomes together with the awareness that migrating cancer stem cell could be the ultimate target for effective therapies offer unprecedented research opportunities. This proposal is designed to seize these opportunities and is focused on understanding the function, regulation and evolution of MCSCs in a multicellular organism. To this end we plan to identify and isolate breast and colon MCSCs by taking advantage of unique reagents, animal models, and technical approaches, and translate the results on large collections of human cancers, disseminating cancer cells, and metastases. The ultimate goal is to describe and functionally analyse the MCSCs and their micro-environment (the MCSC niche) and define a 'MCSC signature', instrumental for the development of future tailor-made therapeutic approaches.

Web site:

not yet

Participants:Coordinator Netherlands Germany Prof. Riccardo Fodde, Josephine Nefkens Institute, Dept. of Pathology, Erasmus University Medical Center Rotterdam, Rotterdam tel: +31 10 4087896 fax: +31 10 4088450 r.fodde@erasmusmc.nl Thomas Brabletz, Laboratory of Molecular Pathology, Department of Pathology, University of Erlangen, Erlangen Christoph Klein, Institut fr Immunologie Ludwig-Maximilians Universitt Mnchen, Institut fr Immunologie Ludwig-Maximilians Universitt Mnchen, Mnchen Alberto Bardelli, Laboratory of Molecular Genetics, The Oncogenomics Center, University of Torino School of Medicine, Fondazione Piemontese per la Ricerca sul Cancro - ONLUS Amministrazione Ricerca, Institute for Cancer Research and Treatment, Candiolo - Torino Manel Esteller, Molecular Pathology Programme / Spanish National Cancer Centre (CNIO) / Cancer Epigenetics Laboratory, Spanish National Cancer Centre, Madrid

Italy Spain

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

MYELOMA STEM CELL NETWORK. A TRANSLATIONAL PROGRAMME IDENTIFYING AND TARGETING THE EARLY MYELOMA CELL HIERARCHYProposal acronym Contract n Duration (starting date) MSCNET LSHC-CT-2006-037602 3 years (01.11.06) EC contribution () Instrument Participants 2.740.000 STREP 9

Abstract:Multiple myeloma is an incurable disease of malignant plasma cells which accumulate in the bone marrow, for which novel and effective therapeutic approaches are vital. The European Myeloma Network (EMN) has recently been set up to investigate this disease, which may serve as a paradigm for incurable cancers. It is our belief that by defining the myeloma stem cell (MSC), this will accelerate our search for a cure for this debilitating disease. Our proposals in pursuit of these aims are based on 3 integrated goals: 1. To establish a structural network with secure funding to underpin our co-ordinated research activities. 2. To formulate a scientific framework to define the MSC and its relationship to the tumor microenvironment. 3. To utilize insight from our scientific investigations to devise therapy, including immunotherapy. For Goal 1, the EMN has set out to interweave European expertise, which is at the forefront of MM research as demonstrated by the high quality of research publications. For Goal 2, the MSCNET has delineated key strengths and limitations in the current state of the art. We will set out an umbrella strategy to examine the key issues relating to the MM stem cell, introducing novel technologies to do so. For Goal 3, it is clearly vital to define the stem or `feeder' cell in MM if the disease is to brought under long-term control or for curative treatment. This remains a pivotal question which will dictate future development of targeted therapy.

Web site:

not yet

Participants:Coordinator Denmark Austria Belgium France Germany Netherlands Spain United Kingdom Prof. Hans Erik Johnsen, Depart. Haematology, Aalborg Hospital, University of Aarhus, Aalborg tel: +45 99 32 68 75 fax: +45 99 32 68 01 h.e.johnsen@dadlnet.dk Niklas Zojer, Wilhelminenkrebsforschungsinstitut des sterreichischen Forums gegen Krebs, Zentrum fr Onkologie und Hmatologie, Wilhelminenspital, Vienna, SME Karin Vanderkerken, Department of Hematology and Immunology, Faculty of Medicine, Vrije Universiteit Brussel, Brussels Bernard Klein, Unit for cellular therapy, institute of research in biotherapy and INSERM, University of Montpellier Friedrich W. Cremer, Myeloma Research Laboratory, Subdepartment Multiple Myeloma, Medical Department V (Hematology and Oncology), University of Heidelberg Pieter P. Sonneveld, Hematology, Erasmus Medical Center and Erasmus University, Rotterdam Nicolaas A. Bos, Dept Cell Biology, Immunology Section, University Medical Center Groningen, Groningen Alberto Orfao, Department of Medicine, Faculty of Medicine and Cancer Research Center, University of Salamanca, Salamanca Surinder Singh Sahota, Molecular Immunology Group, Tenovus Laboratory, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

INTEGRATED FUNCTIONAL GENOMICS IN MUTANT MOUSE MODELS AS TOOLS TO INVESTIGATE THE COMPLEXITY OF HUMAN IMMUNOLOGICAL DISEASEProposal acronym Contract n Duration (starting date) MUGEN LSHG-CT-2005-005203 5 Years (01.01.05) EC contribution () Instrument Participants 11.000.000 NoE 24

Abstract:MUGEN aims, to structure and shape a world-class network of European scientific and technological excellence in the field of 'murine models of human immunological diseases', to advance understanding of the genetic basis of disease and to enhance innovation and translatability of research efforts. MUGEN's specific mission is to bring together different expertise from academic and industrial laboratories in order to study human immunological disease by integrating the participant's strengths in immunological knowledge with new approaches in functional genomics. In this way MUGEN expects to bring Europe a competitive advantage in the development of new diagnostic and therapeutic tools. In concert, MUGEN will promote training of young researchers and exploitation, dissemination and communication of scientific and technological excellence both within and outside of the network, to include all interested stakeholders in the area of human immunological diseases. Instrumental to the realization of these objectives is MUGEN's strong and coherent management framework, which employs a solid organizational infrastructure, and introduces novel network support instruments to achieve effective decision-making and planning. With all these activities, MUGEN will make a significant contribution to the establishment of the European Research Area and to Innovation.

Web site:

http://www.mugen-noe.org

Participants:Coordinator Greece Denmark France Germany Dr George Kollias, Biomedical Sciences Research Center "Alexander Fleming", Vari-Athens tel: +30 210 965 6507 fax: +30 210 965 6563 g.kollias@fleming.gr Jesper Zeuthen, Biomedical Venture, Bankinvest Group, Copenhagen, SME James Di Santo, Institut Pasteur, Paris Bernard Malissen, Centre National de la Recherche Scientifique - Delegation Provence, Marseille Francois Romagne, Innate Pharma Sas, Marseille, SME Werner Muller, German Research Centre for Biotechnology, Braunschweig Manolis Pasparakis & Alvis Brazma, European Molecular Biology Laboratory, Heidelberg Klaus Pfeffer, Heinrich-Heine-Universitat Duesseldorf, Dusseldorf Andreas Radbruch, Deutsches Rheuma-Forschungszentrum Berlin, SME Gunter Hammerling, Deutsches Krebsforschungszentrum, Heidelberg Andreas Persidis, A. Persidis & Sia O.E., Athens

Greece Italy

Netherlands Sweden Switzerland

Giancarlo Fantucci, University of Milano-Bicocca, Milan Paola Ricciardi-Castagnoli, Genopolis, Milan Alberto Mantovani, Istituto di Ricerche Farmacologiche Mario Negri, Milano Glauco Tocchini-Valentini, Consiglio Nazionale delle Ricerche - Istituto di Biologia Cellulare, Monterotondo Scalo Anton Berns, The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Amsterdam Rikard Holmdahl, Lunds Universitet, Lund Bjorn Lowenadler, Arexis Ab, Molndal, SME Maries Van Den Broek, Inst. of Exp. Immunology, University of Zurich Antonio Lanzavecchia, Institute for Research in Biomedicine, Bellinzona Jurg Tschopp, University of Lausanne, Epalinges Martin Bachmann, Cytos Biotechnology Ag, Zurich-Schlieren, SME Lars Fugger, Medical Research Council, London

United Kingdom United States

Klaus Rajewsky, The CBR Institute for Biomedical Research, Inc., Boston

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

MULTI-ORGANISMIC APPROACH TO STUDY NORMAL AND ABERRANT MUSCLE DEVELOPMENT, FUNCTION AND REPAIRProposal acronym Contract n Duration (starting date) MYORES LSHG-CT-2004-511978 5 years (01.01.05) EC contribution () Instrument Participants 12.000.000 NoE 23

Abstract:In Europe over 300.000 people are affected by muscular dystrophies whilst the majority of the aged population are affected by muscle degeneration leading to decreased mobility and loss of independence. This has severe consequences at both a personal and economic level. The aim of this proposal is to understand how these muscular defects can be repaired. Thus, the proposed project will restructure European research and will: i) integrate internationally recognised European specialists working on various aspects of muscle biology and pathology in a number of model organisms; ii) federate their research on well defined aims and obtain a critical mass of researchers who will be able to make significant scientific advancements; iii) create state-of-the-art technical platforms and resources which will serve the network's scientific aims; iv) organize the rapid transfer and application of knowledge acquired in genetically amenable organisms into specific applications for human muscle diseases; v) broadly publicize our scientific action and, through education, attract younger generation of scientists into this essential field of research. All aspects of muscle differentiation are to be investigated and this will be translated into the mechanisms of repair in the adult. Fundamental to the advancement of our knowledge is the recent demonstration that, throughout evolution, many of the molecular mechanisms regulating muscle differentiation have been highly conserved. As molecular pathways can be easily assessed in invertebrates, we will exploit this advantage and rapidly extend the knowledge gained in these systems to determine gene function in higher vertebrates. This is a unique aspect of the proposal and places the consortium at the international forefront of understanding of gene function during normal muscle development and disease.

Web site:

http://www.myores.org

Participants:Coordinator France Czech Republic France Dr. Krzysztof Jagla, Institut National de la Sante et de la Recherche Medicale, INSERM U84, Clermont-Ferrand tel: +33 4 73 17 81 81 fax: +33 4 73 27 61 32 christophe.jagla@u-clermont1.fr Tomas Soukup, Institute of Physiology, Academy of Sciences of the Czech Republic, IPASCR, Department of Functional Morphology, Prague Christophe Marcelle, Centre National de la Recherche Scientifique, UMR6545, Marseille Margaret Buckingham, Institut Pasteur, Departement de Biologie du Developpement, Paris Bernard Thisse, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch Vincent Mouly, Univ. Pierre & Marie Curie, UMR 7000, Cytosquelette et Developpement, Paris Jonathan Dando, INSERM Transfert SA, European project management department, Paris Beate Brand-Saberi, Univ. Klinikum Freiburg, Med. Fak., lnstitut Anatomie Zellbiologie ll, Freiburg Ellen Furlong, European Molecular Biology Laboratory, Developmental Biology and Gene Expression Programmes, Heidelberg Hans-Henning Arnold, Technical University Braunschweig, Cell-and Molecular Biology, Biosciences, Biochemistry and Biotechnology, Braunschweig Renate Renkawitz-Pohl, Philipps-Univ. Marburg, Developmental Biology, Dep. Biology, Marburg Carmen Birchmeier, Max-Delbruck-Centrum fur Molekulare Medizin, Berlin Thomas Braun, Max Planck Gesellschaft, Max Planck Inst., W.G. Kerckhoff-Institut Bad Nauheim Chaya Kalcheim, The Hebrew University of Jerusalem, Dept. of Anatomy and Cell Biology, Faculty of Medicine, Jerusalem Stefano Schiaffino, Univ. Studi di Padova, Dipartimento di Scienze Biomediche Sperimentali, Padova Alberto Ferrus, Consejo Superior de Investigaciones Cientificas, Instituto Cajal, Madrid Philip lngham, Univ. Sheffield, Centre Developm. Genetics, Dep. Biomedical Science, Sheffield Baldjinder Mankoo, King's College London, Randall Centre For Molecular Cell Biology, London Andrea Munsterberg, University of East Anglia, School of Biological Sciences, Cell and Developmental Biology, UEA, Norwich Michael Taylor, University of Wales, Cardiff, Cardiff School of Biosciences, Cardiff John Squire, Imperial College of Science Technology & Medicine, Imperial College London John Sparrow, The University of York, Department of Biology (Area 10), University of York Peter Rigby, The Institute of Cancer Research : Royal Cancer Hospital, London

Germany

Israel Italy Spain United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

CANCER STEM CELLS AND ASYMMETRIC DIVISIONProposal acronym Contract n Duration (starting date) ONCASYM LSHC-CT-2006-037398 3 years (01.10.06) EC contribution () Instrument Participants 2.820.000 STREP 8

Abstract:An intense line of current investigation in cancer is based on the connection between tumorigenesis and stem cell biology. Some tumors may originate from the transformation of normal stem cells at least in the case of blood, breast, skin, brain, spino-cerebellar and colon cancers. In addition, tumors may contain 'cancer stem cells, rare cells with indefinite potential for self-renewal, that drive tumorigenesis. Interestingly, the same signaling pathways (TGF-beta/BMP, Wnt and Notch pathways) appear to regulate self-renewal in stem cells and cancer cells. Self-renewal occurs through the asymmetric cell division of stem cells, which thereby generate a daughter stem cell and another daughter cell that contributes to populate the developing organ or the growing tumor. In the Drosophila nervous system, one of the best understood asymmetric cell division models, asymmetry is mediated by a biased Notchdependent signaling event between the two daughter cells. ONCASYM Partners have recently showed i) that the process of biased signaling during asymmetric cell division is controlled by endocytosis and ii) that tumors can be induced in mutants with altered stem-cell asymmetric division. In human normal and cancer stem cells, asymmetric cell division is supposed to take place, but it has not directly been proved yet. Furthermore, the role of biased signaling by endocytosis in these stem cells has not been addressed to date. The aim of this proposal is 3-fold: i) to screen for genes involved in asymmetric cell division of human cancer stem cells, ii) to characterize the asymmetric cell division of these stem cells by using these candidate genes as markers and developing novel specific biosensors and iii) to functionally study the role of the identified candidate genes during asymmetric cell division of cancer stem cells. Our ultimate goal is to untangle the molecular machinery of cancer stem cell asymmetric division thereby providing drugable targets for cancer therapy.

Web site:

not yet

Participants:Coordinator Germany Marcos Antonio Gonzalez-Gaitan, Max Planck Institute of Molecular Cell Biology and Genetics, Gonzalez-Gaitan Lab, Max-Planck-Gesellschaft zur Frderung der Wissenschaften e.V. represented by the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden tel: +49 351 2102539 fax: +49 351 2101389 gonzalez@mpi-cbg.de Juergen Knoblich, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Richard Janssen, Target Discovery, Galapagos NV, Leiden, Mechelen, IND Carsten Schultz, Gene Expression Programme, Bioorganic Chemistry Lab, European Molecular Biology Laboratory, Heidelberg Pier Paolo Di Fiore, IFOM Fondazione Istituto FIRC di Oncologia Molecolare, IFOM Fondazione Istituto FIRC di Oncologia Molecolare, Milan Umberto Veronesi, Scientific Director's Office, Istituto Europeo di Oncologia Srl, Milan Hans Clevers, Hubrecht Laboratory, Hubrecht Laboratory/KNAW, Utrecht Cayetano Gonzalez, Institut de Recerca Biomedica - IRB, Department of Cell Division, Institut de Recerca Biomedica, Barcelona

Austria Belgium Germany Italy Netherlands Spain

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

PLATFORMS FOR BIOMEDICAL DISCOVERY WITH HUMAN ES CELLSProposal acronym Contract n Duration (starting date) Plurigenes LSHG-CT-2005-018673 3 years (01.01.06) EC contribution () Instrument Participants 2.500.000 STREP 8

Abstract:A first step to regenerative medicine is to find a means to cause controlled de-differentiation of adult tissue. Plurigenes aims at achieving major breakthroughs in the discovery and understanding of the function of genes controlling pluripotency in the central nervous system. These later could enable the de-differentiation of terminally differentiated neural cells into pluripotent cells through transgenesis, a goal that fully meets the requirements of LSH-2004-1.1.0-1. Plurigenes will start by identifying candidate genes in model organisms, following original approaches involving screens performed by in situ hybridations on well characterised neural structures or by gain of function analysis. As pointed out in LSH-2004-1.1.0-1, innovative technologies of transgenesis and imaging in several model organisms will be settled to reach this goal. The project will first characterise in vitro and in vivo the functions of candidate genes involved in the maintenance of pluripotency. On selected genes, it will then validate the possibility to restore the pluripotency of terminally differentiated cells through transgenesis of the candidate genes. Finally, Plurigenes will identify molecular partners and related pathways associated with pluripotency. The project will result in the identification of evolutionarily conserved genes associated with cellular pluripotency; improved methods for transgenesis in fish and ascidians and innovative methods for cell imaging and finally, protocols for the de-differentiation of neural cells.

Web site:

http://www.plurigenes.org

Participants:Coordinator France United Kingdom Dr. Jean-Stphane Joly, Institut de Neurosciences A. Fessard, INRA U1126 "Morphogense du systme nerveux des Chords" & UPR 2197 DEPSN, CNRS, Institut National de la Recherche Agronomique, Gif-sur-Yvette tel: +33 1 69 82 34 31 fax: +33 1 69 82 34 47 joly@iaf.cnrs-gif.fr Patrick Lemaire, LGPD, IBDM UMR6545 CNRS, Universit de la Mditerrane, Centre National de la Recherche Scientifique, Marseille Philippe Genne, Oncodesign, Dijon, SME Joachim Wittbrodt, Developmental Biology Programme, European Molecular Biology Laboratory, Heidelberg Manfred Schartl, Physiological Chemistry I, University of Wuerzburg, Wuerzburg Filomena Ristoratore, Biochemical & Molecular Biology Laboratory, Stazione Zoologica "Anton Dohrn", Napoli Angelo Luigi Vescovi, Dipartimento di Biotecnologie e Bioscienze BTBS, University of Milano Bicocca, Milan Francois Guillemot, National Institute for Medical Research, Division of Molecular Neurobiology, Medical Research Council, London

France Germany Italy

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

ADVANCED GENOMICS INSTRUMENTS, TECHNOLOGY AND METHODS FOR DETERMINATION OF TRANSCRIPTION FACTOR BINDING SPECIFICITIES; APPLICATIONS FOR IDENTIFICATION OF GENES PREDISPOSING TO COLORECTAL CANCERProposal acronym Contract n Duration (starting date) REGULATORY GENOMICS LSHG-CT-2004-512142 4 Years (01.09.04) EC contribution () Instrument Participants 2.200.000 STREP 5

Abstract:Determination of the sequence of the human genome, and knowledge of the genetic code through which mRNA is translated have allowed rapid progress in identification of mammalian proteins. However, less is known about the molecular mechanisms that control expression of human genes, and about the variations in gene expression that underlie many pathological states, including cancer. This is caused in part by lack of information about the 'second genetic code' - binding specificities of transcription factors (TFs). Deciphering this regulatory code is critical for cancer research, as little is known about the mechanisms by which the known genetic defects induce the transcriptional programs that control cell proliferation, survival and angiogenesis. In addition, changes in binding of transcription factors caused by single nucleotide polymorphisms (SNPs) are likely to be a major factor in many quantitative trait conditions, including familial predisposition to cancer. We aim to develop novel genomics tools and methods for determination of transcription factor binding specificity. These tools will be used for identification of regulatory SNPs that predispose to colorectal cancer, and for characterization of downstream target genes that are common to multiple oncogenic TFs. Specific aims: 1. To develop novel high throughput multiwell-plate and DNA-chip based methods for determination of TF binding specificity; 2. To experimentally determine the binding specificities of known cancer-associated TFs; 3. To computationally predict, and to experimentally verify, elements that are regulated by these TFs in genes that are essential for cell proliferation; 4. To develop a SNP genotyping chip composed of SNPs that affect the function of TFbinding sites conserved in mammalian species; 5.To use this chip for genotyping of patients with hereditary cancer predisposition as well as controls in three European populations, for identification of regulatory SNPs associated with cancer.

Web site:

http://research.med.helsinki.fi/regulatorygenomics

Participants:Coordinator Finland Denmark Germany Poland Dr. Jussi Taipale, Helsingin yliopisto, Faculty of Medicine, Molecular & Cancer Biology Research Program, University of Helsinki tel: +358-9-19125556 fax: +358-9-19125554 jussi.taipale@helsinki.fi Torben Falck, Orntoft, Aarhus University Hospital, Skejby, Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Clinical Institute , Aarhus Joerg Hoheisel, Deutsches Krebsforschungszentrum, Functional Genome Analysis, Heidelberg Markus Beier, Magnet 41. VV GmbH, Mannheim, SME Jan Lubinski, Pomeranian Medical University, International Hereditary Cancer Centre, Szczecin

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

SILENCING RNAS: ORGANISERS AND COORDINATORS OF COMPLEXITY IN EUKARYOTIC ORGANISMSProposal acronym Contract n Duration (starting date) SIROCCO LSHG-CT-2006-037900 4 years (01.01.07) EC contribution () Instrument Participants 11.781.445 IP 18

Abstract:A recently discovered layer of gene regulation in eukaryotic organisms employs small regulatory RNAs (miRNAs and siRNAs). These RNAs are 20-28 nucleotides long and are produced by Dicer ribonucleases acting on double-stranded RNA precursors. Together with an effector protein complex, they scan for complementary RNA or DNA so that expression of these targeted molecules is silenced at the transcriptional or posttranscriptional levels. These short RNAs influence gene expression during growth and development and initiate epigenetic changes to DNA and chromatin. SIROCCO will characterize the full complement of miRNAs and siRNAs in animals and plants. Using bioinformatics, genomics, biochemistry, cell biology and genetics, the consortium members will reveal how these RNAs are produced and processed, how they are transported and how they target specific genes and RNAs for silencing. SIROCCO will investigate the miRNA and siRNA profiles associated with development, with phenotypic divergence within populations, and with diseased states including cancer. The functional genomics of silencing RNAs will be addressed by up- or downregulation of miRNA and siRNA species. There will also be an assessment of miRNA and siRNA regulatory networks and their interaction with other cellular control mechanisms. The outputs of SIROCCO will include databases of silencing RNA sequence and function in several organisms, new technologies for detection and manipulation of these RNAs, and information that will allow siRNA and miRNA profiles to be used as molecular markers and diagnostic methods for natural biological variation including the perturbations associated with disease. SIROCCO will also identify potential targets of disease therapy amongst the components of the small RNA silencing systems. Finally, insights generated in SIROCCO will improve the specificity with which small RNAs can be employed as therapeutic tools.

Web site:

http://www.sirocco-project.eu

Participants:Coordinator United Kingdom Denmark France Germany Prof. David Baulcombe, The Sainsbury Laboratory, Norwich tel: +44 1603 450326 fax: +44 1603 450011 david.baulcombe@sainsbury-laboratory.ac.uk Jorgen Kjems, Department of Molecular Biology, University of Aarhus Peter Mouritzen, Exiqon A/S, Vedbaek, SME Annick Harel-Bellan, CNRS UPR 9079, Oncogenese, Differenciation et Transduction du Signal, Centre National de la Recherche Scientifique, Villejuif, Paris Michael Wassenegger, Epigenetics, RLP AgroScience GmbH, AlPlanta-Institute for Plant Research, Neustadt Detlef Weigel, Department of Molecular Biology, Max Planck Institute for Developmental Biology, Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V., Tubingen, Munchen Stephen Cohen, Developmental Biology Programme, European Molecular Biology Laboratory, Heidelberg Jozsef Burgyan, Institute of Plant Biology, Molecular Virology Group, Agricultural Biotechnology Center, Godollo Zvi Bentwich, Rosetta Genomics Ltd, Rehovot, SME Irene Bozzoni, Dipartimento di Genetica e Biologia Molecolare, RNA lab., Universita di Roma Roberto Di Lauro, CEINGE Biotecnologie Avanzate S.C.a r.l., Naples Ronald Plasterk, Hubrecht Laboratory / KNAW, Utrecht Xavier Estivill, Genes and Disease Programme, Centre de Regulacio Genomica, Barcelona Witold Filipowicz, Friedrich Miescher Institute, Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute for Biomedical Research, Basel Eric Alexander Miska, Wellcome Trust/Cancer Research UK Gurdon Institute, The Chancellor, Masters and Scholars of the University of Cambridge Caroline Dean, Department of Cell and Developmental Biology, John Innes Centre, Norwich Gyorgy Hutvagner, Division of Gene Regulation and Expression, Faculty of Life Sciences, University of Dundee Tamas Dalmay, School of Biological Sciences, University of East Anglia, Norwich

Hungary Israel Italy Netherlands Spain Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

EPIGENETIC PLASTICITY OF THE GENOMEProposal acronym Contract n Duration (starting date) THE EPIGENOME LSHG-CT-2003-503433 5 years (01.06.04) EC contribution () Instrument Participants 12.500.000 NoE 18

Abstract:In this 'post-genomic' era, advances in epigenetic research represent a new frontier that is predicted to yield novel insights for gene regulation, cell differentiation, stem cell plasticity, organismal development, human diseases, cancer, infertility and aging. A central emerging concept proposes that there is an epigenetic code, which considerably extends the information potential of the genetic code. Thus, one genome can generate many epigenomes as the fertilised egg progresses through development and translates its information into a multitude of cell fates. Epigenetic research touches on many topics of key interest to the general public, including embryonic and adult stem cells, and is anticipated to have far-reaching implications for medicine and the understanding of the basic processes of cell fate determination. The resulting developments will undoubtedly impact academic and industrial research communities and will form an important knowledge base for policy makers and public bodies that contribute to the socio-economic future of our 'post-genomic' society. Europe has many world-leading laboratories in epigenetic research. This Network of Excellence (NoE) proposes to follow a progressively expanding strategy. For its initial establishment, 25 teams from 18 different institutions with a proven record as leaders in their field, will constitute a virtual core centre to combine their expertise and resources. An immediate structuring role is provided by the concentration of most of these 25 teams around 8 established centres of epigenetic research. In defining a coordinated joint programme of activities (JPA), this NoE will assimilate existing synergies for building a structure that can feed three important needs: to advance scientific discoveries, integrate European research and establish an open dialogue. To achieve these three goals, the core NoE will make 50% of the grant available for network development and the durable shaping of a coherent European Research Area (ERA) on epigenetic research.

Web site:

http://www.epigenome-noe.net

Participants:Coordinator Austria Austria France Germany Prof. Thomas Jenuwein, Research Institute for Molecular Pathology, Vienna tel: +43 1 79 73 04 74 fax: +43 1 79 8 71 53 jenuwein@imp.univie.ac.at Denise Barlow, Research Center for Molecular Medicine, Vienna Genevive Almouzni, Institut Curie, Paris Philip Avner, Institut Pasteur, Paris Renato Paro, Ruprecht Karls-University Heidelberg Ingrid Grummt, German Cancer Research Center, Heidelberg Jrn Walter, Saarland Universty, Saarbrcken Peter Becker, Ludwigs-Maximilians-University Munich Gunter Reuter, Martin Luther-University Halle-Wittenberg, Halle (Saale)

Netherlands Switzerland United Kingdom

Frank Grosveld, Erasmus Medical Center Rotterdam Susan Grasser-Wilson, University of Geneva Ueli Grossniklaus, University of Zurich Robin Allshire, The University of Edinburgh Amanda Fisher, Medical Research Council, London Bryan Turner, The University of Birmingham Wolf Reik, Babraham Institute, Cambridge Azim Surani, University of Cambridge Peter Meyer, The University of Leeds

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

NOVEL TOOL FOR HIGH-THROUGHPUT CHARACTERIZATION OF GENOMIC ELEMENTS REGULATING GENE EXPRESSION IN CHORDATESProposal acronym Contract n Duration (starting date) TRANSCODE LSHG-CT-2004-511990 3 years (01.01.05) EC contribution () Instrument Participants 1.000.000 STREP 5

Abstract:The aim of this project is to develop open source tools enabling to identify in silico potential cis-regulatory modules, as well as the transcription factors (TF) that bind to them. A publicly available genomic resource describing TF across chordate genomes, including mammals, fish and ascidians, will be developed. Based on this resource, large-scale sequence comparisons of orthologous non-coding regions of TF genes will be performed. Moreover, a comprehensive invitro study of DMA-binding affinity of TF proteins will be used to build novel models of TF binding sites. Thus multidisciplinary approaches will be developed to identify the cis-regulatory regions driving TF gene expression. The basic steps undertaken will be: 1. Genome wide census and phylogenetic analysis of all TFs in sequenced chordate genomes. 2. Genome wide identification of Multi Species Conserved Sequences (MCSs) within orhtologous non-coding regions of chordate TFs. 3. Characterization of the activity of the identified MCSs in Ciona and zebrafish embryos, mammalian cells as well as in transgenic mice. 4. Training of a novel algorithm to predict and characterize MCSs active in various model systems. 5. Comprehensive determination of the in vitro DMA-binding specificity of all transcription factors in a chordate genome. 6. Building novel bioinformatics models of TF binding sites based on complex grammars such as Hidden Markov Models and Stochastic Context Free Grammar. 7. Integration of all the above data into a publicly available, open source bioinformatics tool that can be used either via the project website or downloaded for large-scale projects. This project represents a large-scale pluri-disciplinary effort to decipher the grammar of chordate regulatory sequences, and will have a strong impact by building tools and resources that will enable to devise more sophisticated hypothesis regarding regulatory networks, especially those of TFs which are involved in fundamental biological processes.

Web site:

http://www.transcode.tigem.it

Participants:Coordinator Italy France Germany Italy United Kingdom Dr. Elia Stupka, Fondazione Telethon, Telethon Inst. Genetics and Medicine (TIGEM), Naples tel: +390816132335 fax: +390816132351 elia@tigem.it Patrick Lemaire, Centre National de la Recherche Scientifique, LGPD, IBDM UMR6545, Marseille Ferenc Muller, Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, EggensteinLeopoldshafen Graziano Pesole, Univ. Milano, Dipartimento di Scienze Biomolecolari e Biotecnologie, Milan Samuel Aparicio, University of Cambridge, Department of Oncology, Hutchison-MRC Research Institute, Cambridge

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

DEVELOPING Tools for new therapies and medicines

20

MODULATION OF THE RECRUITMENT OF THE VESSELS AND IMMUNE CELLS BY MALIGNANT TUMORS: TARGETING OF TUMOR VESSELS AND TRIGGERING OF ANTI-TUMOR DEFENSE MECHANISMSProposal acronym Contract n Duration (starting date) Anti-tumor targeting LSHC-CT-2005-518178 3 years (01.11.05) EC contribution () Instrument Participants 2.420.000 STREP 8

Abstract:All malignant tumors acquire the capacity for efficient recruitment of blood vessels, which are absolutely necessary for tumor growth beyond a certain size. They also frequently stimulate lymphangiogenesis supporting dissemination of tumor cells not only via the blood vasculature, but in addition via the lymphatic system leading to metastasis. Vessel growth is promoted by sprouting angiogenesis and the homing of bone marrow progenitor cells into the tumors and tumor vessels. The extensive vascularization facilitates the invasion of cells of the innate and adaptive immune system, which however stay largely functionally suppressed by the tumor environment and even contribute to angiogenesis and tumor growth by cytokine and growth factor secretion. We propose in this application i) to further investigate key regulatory pathways by which tumor-secreted molecules promote vascularization and inhibit immune cell function, ii) to develop methods to inhibit tumor growth and metastasis by blocking vessel and tumor cell growth, and iii) to achieve tumor clearance by additionally promoting activation and homing of functional immune cells to the tumors. The project will comprise the collaboration of laboratories with complementary expertise. It will include experts in blood vessel and lymph vessel angiogenesis, metastasis formation, progenitor cell incorporation into tumors and tumor vessels, anti-tumor defense mechanisms of the immune system and viral transduction techniques. The final goal will be the preclinical evaluation of strategies in murine models of three of the most prevalent forms of human cancer, i.e. carcinomas of the breast, colon and prostate. The strategies to target the tumor will be based on gene, cell and immune therapy methods. They will include the use of i) adenoviruses for the expression of angiogenesis inhibitors following targeted delivery of the viruses to the tumor vasculature, ii) the genetic modification of murine embryonic and human umbilical cord/bone marrow progenitor cells and their directed homing into the tumor and iii) the use of genetically engineered immune cell products or the transduction of immune cells to activate targeting of the tumors by innate and adaptive anti-tumor defense mechanisms. We expect that this project will contribute to innovation on three levels. Firstly, we will gain basic additional novel knowledge on important pathways and regulatory molecules for the recruitment of host cells to the tumors and their functional interaction with the tumor. Secondly, we will use this knowledge to test novel ways of targeting viruses and (transduced) cells to the tumors. Finally, we will evaluate whether by a combination of anti-angiogenesis therapy with directed anti-tumor immunotherapy it would be possible not only to inhibit tumor growth, but to eradicate residual disease.

Web site:

not yet

Participants:Coordinator Austria Austria Germany Israel Netherlands Switzerland Prof. Erhard Hofer, Medical University Vienna, Department of Vascular Biology and Thrombosis Research Center for Biomolecular Medicine and Pharmacology, Vienna tel: +43 142 776 2553 fax: +43 142 776 2550 Erhard.hofer@meduniwien.ac.at Karl-Heinz Preisegger, EccoCell Biotechnologie GmbH, Graz, SME Antonis Hatzopolous, Gesellschaft fr Strahlenforschung, Munic Alexander H. Enk & Karsten Mahnke, University of Heidelberg, Depart. Dermatology, Heidelberg Melvyn Little, Affimed Therapeutics AG, Heidelberg, SME Ofer Mandelboim, The Hebrew University of Jerusalem, Lautenberg Center for General and Tumor Immunology Hebrew-University-Hadassah Medical School, Jerusalem Hidde Haisma, University Groningen, Department of Therapeutic Gene Modulation University Centre of Pharmacy, Groningen Michael Detmar, Swiss federal Institute of Technology, Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences, Zurich

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

CONCERTED SAFETY & EFFICIENCY EVALUATION OF RETROVIRAL TRANSGENESIS IN GENE THERAPY OF INHERITED DISEASESProposal acronym Contract n Duration (starting date) CONSERT LSHB-CT-2004-005242 4 Years (01.11.04) EC contribution () Instrument Participants 11.635.000 IP 20

Abstract:CONSERT will integrate leading European activities for a structured implementation of novel therapies using genetically enhanced postnatal stem cells, with focus on the treatment of monogenic immunodeficiencies, hemoglobinopathies, anemias and storage disorders. CONSERT will develop and evaluate methods for genetic stem cell modification with wide implications for many other disorders including viral infection and cancer. A central and exceptional theme of our work is an unbiased safety and efficiency evaluation of the key technology used in the genetic modifications of replicating somatic cells: retroviral vector-mediated transgenesis. This is only possible through concerted multi-center studies. Lenti, spuma- and gammaretroviral vectors will be tailor-made for target disorders and tested for potency and safety in preclinical disease models. Designed with a translational aim, basic studies in stem cell biology and selectable marker technology will complement this research. A unique and most important aspect of CONSERT is the molecular and clinical monitoring of currently active and successful clinical trials of genetic therapies. This will create a paradigmatic data-mining activity to obtain insights into crucial issues of clonal kinetics of gene-modified cells in vivo. In parallel, molecular studies in precise cell systems and animal models will provide a deeper mechanistic understanding of transgene-host interactions. This project will create a perfect basis for technology development and simultaneously promote patient safety. Translational dissemination of know-how from academia to industry will create a network of cell processing manufacturers with large economic potential, and prepare future clinical studies with improved predictability. Supervised by a proactive ethical project, CONSERT will stimulate a competitive and complementary evolution of biomedical academia, clinics, innovative health service providers, and associated training opportunities.

Web site:

http://www.genetherapy.nl

Participants:Coordinator Netherlands France Prof. Gerard Wagemaker, Erasmus University Medical Center Rotterdam, Institute of Hematology, Rotterdam tel: +31 10 408 7766 fax: +31 10 408 9470 g.wagemaker@erasmusmc.nl Francois-Loic Cosset, Alain Fisher & Marina Cavazzana-Calvo, Institut National de la Sante et de la Recherche Medicinale, INSERM U412 - LVRTG, Lyon & INSERM U429, Hopital Necker, Paris Olivier Danos, Genethon, Evry, France William Saurin, Genomining, Montrouge, SME Christopher Baum, Medizinische Hochschule Hannover, Dept. of Hematology, Hemostaseology and Oncology, Laboratory of Experimental Cell Therapy, Hannover Christof von Kalle, Universitaet klinikum, Institute for Molecular Medicine and Cell Research, Stem Cell Biology Lab, Freiburg Klaus Kuehlcke, Europaeisches Institut fur Forschung und Entwicklung von Transplantationsstrategie AG, Idar-Oberstein, SME Michael Fuchs, Institut fur Wissenschaft und Ethik e.V., Section Biomedical Ethics, Bonn Thomas M. Pohl, GATC Biotech AG, Konstanz, SME Nicholas Anagnou & George Vassilopoulos, Univ. Athens School Medicine, Lab. Biology, Athens Fulvio Mavilio, Molecular Medicine S.p.A., Milan, SME Luigi Naldini, Fondazione Centro San Raffaele del Monte Tabor, DIBIT-TIGET, Milan Maria Grazia Roncarolo, Universita Vita-Salute San Raffaele, Faculty of Medicine, Milan Louise van den Bos, Science & Technology Transfer (S&TT), Rotterdam, SME

Germany

Greece Italy Netherlands Spain

Sweden Switzerland United Kingdom

Jordi Barquinero, Centre de Transfusio i Banc de Teixits, Unitat de Diagnostic i Terapia Molecular, Barcelona Juan M. Bueren, Centro de Investigaciones Energeticas Mediambientales Y Technologicas, Hematopoiesis Program, Madrid Stefan Karlsson, Lunds Universitet, Medical Faculty, Molecular Med. and Gene Therapy, Lund Didier Trono, Univ. Geneva, Fac. Medicine, CMU, Depart. Microbiology & Mol. Med., Geneva Adrian Trasher & Mary Collins, Inst. Child Health & Univ. College London, London Lez Fairbairn, University Manchester, Dept. of Cancer Studies, Christie Hospital, Manchester

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

CRYO-BANKING OF STEM CELLS FOR HUMAN THERAPEUTIC APPLICATIONProposal acronym Contract n Duration (starting date) CRYSTAL LSHB-CT-2006-037261 3 years (01.02.07) EC contribution () Instrument Participants 2.400.000 STREP 7

Abstract:Stem cells are at the centre of biomedical research. The development of human stem cell therapies will have to build on a safe and reliable supply of human stem cells which must be assured by cell banking. Currently, the isolation, identification and culture of stem cells are not standardised between laboratories, and reproducibility of protocols is limited. Today's banking approaches still rely on storing sources of stem cells rather than on banking of defined, well-characterised stem cell populations (both adult and embryonic). Cryopreservation of stem cells itself is not yet optimised and validated for the different cell types, and multiple cell biological and biophysical challenges remain to be addressed in order to define optimised cryopreservation protocols. The problems currently limiting the routine application of stem cell banking with a therapeutic perspective will be addressed by the CRYSTAL project. The consortium will develop tools and optimised procedures to enable cryopreservation of different stem cell types and allow safe production of sufficient numbers of high-quality cells for future human therapy. This will comprise standardised protocols and tools for stem cell isolation, identification and culture, novel approaches to their cryopreservation (e.g. novel cryoprotectants, freezing in different conformations) and an automated quality control system for stem cell preparations. Five stem cell research laboratories providing four different sources of adult (from cord blood, bone marrow and placenta) and human embryonic stem cells have teamed with two partners specialising in applied banking and fundamental cryobiological research. CRYSTAL is thus in a position to solve existing problems in an integrated, systematic approach and to provide standardised, reproducible methods and tools to advance therapeutic stem cell research in Europe.

Web site:

not yet

Participants:Coordinator Germany Austria Belgium Germany Netherlands Switzerland Prof. Jrgen Hescheler, Institute of Neurophysiology, University of Cologne tel: +49-221-4786960 fax: +49-221-4783834 j.hescheler@uni-koeln.de & j.winkler@uni-koeln.de Andrea Kolbus, Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Department of Obstetrics and Gynecology, Vienna Catherine Verfaillie, Hematology Section, Katholieke Universiteit Leuven, Leuven Peter Ponsaerts, University Hospital Anwerp, Laboratory of Experimental Hematology, University of Antwerp, Edegem Heiko Zimmermann, Fraunhofer-Institut fr Biomedizinische Technik, St. Ingbert, Mnchen Guy Wouters, Cryo-Save-Labs, Life-Sciences Group NV, Mechelen, Zutphen, SME Andreas Hugo Zisch, Obstetrics, University Hospital Zurich, University Zurich

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

EUROPEAN EMBRYONAL TUMOR PIPELINEProposal acronym Contract n Duration (starting date) E.E.T.-Pipeline LSHC-CT-2006-037260 3 years (01.01.07) EC contribution () Instrument Participants 4.000.000 STREP 13

Abstract:Treatment of embryonal tumors (ET) is a challenge for the pediatric oncologist. Innovative translational research is required to exploit available genomic data and implement state-of-the-art technologies to overcome the deficits of current diagnostic and treatment strategies. We will set up a consortium of leading European institutions and SMEs with extensive clinical and technological expertise to establish a unique pipeline for the comprehensive development and validation of novel diagnostic tools in addition to efficient preclinical drug development for ET. Our holistic approach includes: 1) Validation of a chip-based diagnostic platform tailored specifically for ET including analysis of genes previously shown by the consortium to be affected in ET 2) Generation of ET-specific data on novel array-based platforms for the development of diagnostics at the microRNA and serum proteomics levels 3) Extension of an existing database designed to warehouse complete clinical and experimental data for neuroblastoma to include all ET entities 4) Implementation of a virtual ET-Biobank to improve sharing of patient samples 5) Functional characterisation of the most promising molecular targets previously identified by the partners as a foundation for entry into a drug development pipeline 6) Integration of existing disease-specific mouse models to evaluate new treatment modalities in vivo 7) Initial evaluation of screening methods for small molecules and antibodies affecting ET cell growth 8) Application of novel bioinformatic solutions for the meta-analyses 9) Dissemination of the novel tools to researchers and clinical study centers in Europe Our coordinated effort can achieve the critical mass to facilitate the necessary integration of research capacities for translating ET genome data into significant medical progress. Involvement of clinical study centers will ensure a direct link to the bedside, aimed at improving child health and quality of life.

Web site:

not yet

Participants:Coordinator Germany Austria Belgium France Germany Italy Norway Slovenia Switzerland Prof. Angelika Eggert, Pediatric Oncology, University Hospital of Essen tel: +49 2017233755 fax: +49 2017235750 angelika.eggert@uni-essen.de Heinrich Kovar, Children's Cancer Research Institute, Vienna Chris Roelant, Memobead Technologies, Boom, SME Frank Speleman, Centre for Medical Genetics, Ghent University, Ghent Olivier Delattre, Unite 509 Inserm, Institut Curie, Paris Joe Lewis, Chemical Biology Core Facility, European Molecular Biology Laboratory, Heidelberg Manfred Schwab, Tumour Genetics, German Cancer Research Center, Heidelberg Roland Eils, Division of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg Alessandro Bulfone, bio))flag Srl, Pula, SME Massimo Zollo, CEINGE-BIOTECNOLOGIE AVANZATE S.C. a.r.l., Naples Bjrn Cochlovius, Affitech AS, Oslo, SME

Saso Dzeroski, Department of Knowledge Technologies, Jozef Stefan Institute, Ljubljana Michael Grotzer, Department of Oncology, University Children's Hospital of Zurich

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

EPISOMAL VECTORS AS GENE DELIVERY SYSTEMS FOR THERAPEUTIC APPLICATIONProposal acronym Contract n Duration (starting date) EPI-VECTOR LSHB-CT-2004-511965 3 years (01.01.05) EC contribution () Instrument Participants 2.100.000 STREP 8

Abstract:Many chronic human diseases cause great suffering as a result of inherited and sporadic genetic mutations. Gene therapy provides therapeutic benefit if a normal copy of the affected gene can be expressed in appropriate target cells. Retroviruses are often used for gene delivery, as the therapeutic gene integrates into a host cell chromosome. As integration is targeted to active chromatin this ensures long-term expression. However, this can disrupt gene expression at the integration site and lead to cancer. We propose that safe DNA vectors for human gene therapy must deliver therapeutic levels of gene expression without altering patterns of expression in the host cells. Extra-chromosomal gene expression vectors provide the best way of achieving this. Results will provide novel DNA vectors and protocols that will be used as gene delivery systems for therapeutic application. Expression vectors will be developed using rational design parameters that incorporate existing knowledge of genetic and epigenetic factors that regulate chromatin function in mammalian cells. DNA vectors will be designed specifically for ectopie gene expression from extra-chromosomal loci in the host cells, to provide regulated gene expression for safe, efficient and sustained gene therapy. Extra-chromosomal gene expression vectors will be validated for human gene therapy in a pre-clinical setting and protocols for clinical application established. Prototype extra-chromosomal gene expression systems that provide efficient and sustained gene expression will be refined to develop second-generation gene therapy vectors. We will use a systematic analysis of genetic elements to define design parameters for rational vector construction. The performance of second-generation gene expression vectors will be validated for human gene therapy in a pre-clinical setting and protocols for clinical application will be established using myocytes, hepatocytes and haemotopoeitic stems cells as model systems.

Web site:

http://www.ls.manchester.ac.uk/epivector

Participants:Coordinator United Kingdom Germany Israel Netherlands Spain United Kingdom Dr. Dean A. Jackson & Dr. Anne-Marie Buckle, Faculty of Life Sciences, University of Manchester tel: +44 1612 004 255 +44 161 306 4214 fax: +44 1612 360 409 dean.jackson@umist.ac.uk a.buckle@manchester.ac.uk Hans Joachim Lipps, University of Witten, Institute for Cell Biology, Witten Juergen Bode, GBF, German Research Center for Biotechnology, Braunschweig Ben Davies, GenOway GmbH, Hamburg, SME Ariella Oppenheim, The Hebrew University of Jerusalem, Dept. of Hematology, Hebrew University-Hadassah Medical School, Jerusalem Roeland Van Driel, Univ. Amsterdam, Swammerdam Institute for Life Sciences, Amsterdam Fernando Azorin, Consejo Superior de Investigaciones Cientificas, Department of Molecular and Cellular Biology - Instituto de Biologia Molecular de Barcelona John George Dickson, Royal Holloway & Bedford New College - University of London, Centre for Biological Sciences, Egham, Surrey

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

NOVEL APPROACHES TO PATHOGENESIS, DIAGNOSIS AND TREATMENT OF AUTOIMMUNE DISEASES BASED ON NEW INSIGHTS INTO THYMUS-DEPENDENT SELF-TOLERANCEProposal acronym Contract n Duration (starting date) EURO-THYMAIDE LSHB-CT-2003-503410 5 years (01.01.04) EC contribution () Instrument Participants 12.000.000 IP 25

Abstract:Autoimmune diseases are a significant burden for the quality of life and health care cost. Despite intense research efforts, the mechanisms underlying the development of autoimmune diseases are still largely obscure. This obvious ignorance explains why the current treatment of these chronic diseases remains inadequate and is associated with severe side effects. Here we propose an original and new approach to tackle this problem. Our approach is mainly based on the major biological function of the thymus, i.e. to ensure the generation of a diverse repertoire of T cell receptors that are selftolerant. The thymus achieves this goal by using two complementary mechanisms: a) apoptotic deletion and developmental arrest of T cells bearing a receptor (TCR) with high affinity for self-antigens presented by major histocompatibility complex (MHC) proteins expressed by thymic epithelial and dendritic cells, and b) generation of selfantigen specific regulatory T cells. The escape from central self-tolerance now appears to play a prominent role in the development of autoimmune diseases. Six workpackages will achieve the objectives of this proposal: 1. Intrathymic promiscuous gene expression and self-peptide tolerogenic therapy. 2. Preclinical studies of the autoimmune regulator (AIRE) in gene therapy. 3. Interest of anti-Coxsackievirus B4 vaccination for prevention of type 1 diabetes. 4. Exploration of a new T cell pathway governing autoimmunity and allergy. 5. Development, function and therapeutic utility of regulatory T cells in autoimmune diseases and asthma. 6. Evaluation of thymic epithelial stem cell therapeutic potential. This ambitious research project will lead to new insights into disease mechanisms, and will concurrently provide a unique platform for innovative diagnostics and for disease-specific therapy aimed at a cure and prevention of autoimmune diseases, such as type 1 diabetes as a prototypic target of this proposal.

Web site:

http://www.eurothymaide.org

Participants:Coordinator Belgium Austria Australia Belgium Canada Estonia Finland France Germany Prof. Vincent G. Geenen, University of Liege tel: +32 4 366 25 50 fax: +32 4 366 29 77 vgeenen@ulg.ac.be Ludger Klein, Research Institute of Molecular Pathology, Vienna Josef Penninger, Inst. of Molecular Biotechnology of The Austria Academy of Sciences, Vienna Josef Penninger, Apeiron Biologics, Vienna, SME Hamish S. Scott, The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria

Alain Bosseloir, Zentech, Angleur, SME David Muntz, Euro Top, Brussels, SME Rafick-Pierre Sekali, Universit de Montral Part Peterson, University of Tartu Minna Valtavaara, FIT Biotech Oyj Plc, Tampere, SME Philippe Naquet, Centre National De La Recherche Scientifique, Marseille Didier Hober, Centre Hospitalier Rgional et Universitaire de Lille Joost van Meerwijk, Institut National de la Sante et de la Recherche Medicale, Toulouse Bruno Kyewski, Deutsches Krebsforschungszentrum (German Cancer Res. Center), Heidelberg Alexander Marx, Bayerische Julius Maximilians-Universitat Wurzburg Thomas Boehm, Max-Planck-Society for the Advancement of Science, Max-Planck-Institute of Immunobiology, Freiburg Lutz Zeitlmann, Ingenium Pharmaceuticals Ag, Martinsried, SME Isabella Screpanti, Dipartimento di Medicina Sperimentale e Patologia (DMSP) Universita Degli Studi Di Roma - La Sapienza Ricardo Pujol-Borrell, Lab. Immunobiology for Research and Applications to Diagnosis (LIRAD), Institute Germans Trias & Pujol for Research in Health Sciences (IGTP), U. A. Barcelona Dolores Jaraquemada, Laboratory of Cellular Immunology, Institut de Bioteccnologia i Biomedicina (IBB), Universita Autonoma de Barcelona Georg A. Hollander, University of Basel Antonius Rolink, University of Basel Fiona Powrie, Chancellor Masters and Scholars of the University of Oxford Catherine Martha Hawrylowicz, Kings College London Eric John Jenkinson, University of Birmingham

Italy Spain

Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

TARGETING CANCER STEM CELLS FOR THERAPYProposal acronym Contract n Duration (starting date) EuroCSC LSHC-CT-2006-037632 3 years (01.01.07) EC contribution () Instrument Participants 1.900.000 STREP 6

Abstract:Cancer remains one of the leading causes of death in the Western world, and while chemotherapy has provided a major improvement in survival for a wide array of malignant diseases lethality remains high in most cancers and side-effects are severe, and include developmental impairment, when used in childhood malignancies, infertility as well as damage to nonmalignant tissues with resulting diminished quality of life for a large proportion of survivors. Recently, the realization that several tumour types contain rare populations of cancer stem cells (CSCs), which are capable of reforming the tumour upon transplantation while their progeny are not, have opened the possibility of using CSCs as targets for directed molecular therapies that could lead to improved tumour eradication as well as reduced side effects of treatment. The goal of the present project is to perform a thorough characterization of AML, cALL and breast cancer CSCs, as well as a systematic comparison of these with their normal stem cell and progenitor counterparts using gene profiling, to identify putative molecular targets in CSCs. In parallel, we will use mouse genetic modelling to obtain information about genes regulated by oncogenic changes in stem- and progenitor cell populations. Directly oncoprotein-regulated CSC targets will be validated in vitro and, where relevant, in vivo. Finally, we will screen small molecule libraries for compounds that antagonize leukemogenic oncoproteins in efficient zebrafish models. These compounds will be tested for activity in mammalian assays, screened against the putative targets identified by gene profiling, and used to affinity-purify additional interacting proteins. The final outcome will be a set of identified and validated CSC molecular targets, and a corresponding collection of small molecule inhibitors with activity against the effects of leukemogenic oncoproteins on hematopoietic stem cell/progenitor populations.

Web site:

not yet

Participants:Coordinator Germany Denmark Sweden United Kingdom Dr. Claus Nerlov, Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo (Italy), Heidelberg tel: +39 06 9009 1218 fax: +39 06 9009 1272 nerlov@embl-monterotondo.it Ole William Petersen, Structural Cell Biology Unit, Department of Anatomy, The Panum Institute, University of Copenhagen, Copenhagen Sten Eirik Jacobsen, Lund Strategic Center for Stem Cell Biology and Cell Therapy, Medical Faculty, Lunds Universitet, Lund Dominique Bonnet, Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London Roger Patient, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, Medical Research Council, Headington, London Jon Tinsley, VASTox plc, Abingdon, SME

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

EUROPEAN CONSORTIUM FOR STEM CELL RESEARCHProposal acronym Contract n Duration (starting date) EUROSTEMCELL LSHB-CT-2003-503005 4 years (01.02.04) EC contribution () Instrument Participants 11.906.400 IP 14

Abstract:The goal of the 4-year project is to develop an advanced technological platform for new cell based therapies and create a foundation for translational research in the stem cell field. The project draws together the capabilities of 11 academic centres and 3 industries in 8 European countries, with expertise encompassing transgenesis, stem cell biology, developmental biology, tissue repair, in vivo disease models and clinical cell transplantation. The key aim is to develop well-characterized cell lines of therapeutic potential derived from stem cells of embryonic, neural, mesodermal and epithelial origin. The breadth and scale of this project are unprecedented in the stem cell field worldwide and will enable for the first time a systematic comparative evaluation of the properties and therapeutic potential of stem cells of embryonic, foetal and adult origin. The research is organized in 7 Work Packages: Identification and Isolation (WP 1), Lineage Analysis and Differentiation Potential (WP 2), Self-Renewal and Upscaling (WP 3), Control of Differentiation (WP 4), Application in Neurological Disease (WP 5), Muscle Repair (WP 6) and Epidermal Repair (WP 7). Spanning the work packages are three Flagship Projects aimed at Generation of new antibody reagents against stem cells (FSP 1), development of a prototype European Stem Database and Stem Cell Repository (FSP 2), and a Forum for Ethics and Social Issues related to stem cell research (FSP 3). A pan-European Training Program will promote interdisciplinary and trans-European collaboration and technology transfer, and stimulate the recruitment of young scientists and clinical researchers to the stem cell field. Three industries are fully integrated in the programme and an IPR Management Team will ensure that intellectual property and commercial exploitation are professionally handled. In summary, the EuroStemCell consortium brings together the leading investigators across Europe to create a team unmatched in quality.

Web site:

http://www.eurostemcell.org

Participants:Coordinator United Kingdom Denmark France Germany Italy Sweden Switzerland United Kingdom Prof. Austin Smith, The University of Edinburgh, Scotland tel: +44 131 650 5890 fax: +44 131 650 7773 austin.smith@ed.ac.uk Lars Wahlberg, NsGene A/S, Ballerup, SME Margaret Buckingham, Institut Pasteur, Paris Olivier Brstle, University of Bonn Medical Center Giulio Cossu, Fondazione Centro San Raffaele del Monte Tabor, Milano Elena Cattaneo, Universita' degli Studi di Milano, Milano Claus Nerlov, European Molecular Biology Laboratory, Monterotondo Anders Bjrklund, Lunds Universitet Urban Lendahl, Karolinska Institutet, Stockholm Katarina Jansson, Neuronova AB, Stockholm, SME Yann Barrandon, Swiss Federal Institute of Technology Lausanne

Fiona Watt, Cancer Research UK, London John McCafferty, Genome Research Ltd, London Timothy Allsopp, Stem Cell Sciences UK Ltd, West Lothian, SME

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

TARGETING NEWLY DISCOVERED OXYGEN-SENSING CASCADES FOR NOVEL CANCER TREATMENTS BIOLOGY, EQUIPMENT, DRUG CANDIDATESProposal acronym Contract n Duration (starting date) EUROXY LSHC-CT-2003-502932 5 years (01.02.04) EC contribution () Instrument Participants 8.000.000 IP 21

Abstract:The last decade's basic and clinical oncology research has revealed a number of so far unrecognised regulating responses (e.g. HIF-1) in cells exposed to hypoxia. These processes have been proven highly important for tumour progression and resistance to radiotherapy and certain types of chemotherapy. Because of their strong over-expression in solid cancer tumours in comparison to adjacent normal tissue, this new knowledge may open a therapeutic window for cancer treatment targeting hypoxia-responsive processes. Major EU stakeholders in academic research and industry will therefore explore and validate these new molecular targets as a necessary step in the preclinical development of innovative new diagnostics and treatment. Our editing committee found it necessary to go over all aspects of the total task in order to plan the initial work correctly and feel that evaluators will have the same need. We therefore present tightly structured and fully described workpackages for all five years. Our committee has identified the outstanding basic problems to be solved over the first 2 to 3 years in order to allow a successful drug development. These include: dissection of relevant steps in cancer cell response to hypoxia, development of the technology platform needed, and further identification and characterisation of marker/target molecules. Our own mid-term evaluation will then select which hypoxic processes may be suitable as targets for cancer- specific treatment. After this, we will study diagnostic tagging and therapeutic strategies leading up to a selection process of promising compounds to be further developed. The new treatments will be developed along two lines: targeting known cytostatics towards the newly discovered hypoxiaresponsive molecules and searching for so far unused compounds, preferably toxic to pathways active during hypoxia. The final effort will be to ensure continued industry utilisation of our results.

Web site:

http://www.funding.aau.dk/goingproj.htm

Participants:Coordinator Denmark Denmark France Germany Prof. Peter Ebbesen, Aalborg Universitet, Laboratory for Stem Cell Research, Aarhus C tel: +45 861 273 66 fax: +45 861 954 15 ebbesen@lsr.auc.dk Peter Mosborg Petersen, Vivox ApS, Aarhus, SME Anders B. Damholt, Leo Pharma AS, Ballerup, SME Marie-Christine Multon, Aventis Pharma, Vitry-sur-Seine, IND Martina Rimmele, RiNA-Netzwerk RNA Technologien GmbH, Berlin Alfons Krug, LEA Medizintechnik GmbH, Giessen, SME Jobst Gerhard, Jobst Technologies GmbH, IND Agnes Grlach, Deutsches Herzzentrum Mnchen Kai-Uwe Eckardt, University of Erlangen-Nuremberg, Division of Nephrology and Hypertension, Erlangen Andrea Scozzafava, University of Florence Arvydas Kanopka, Institute of Biotechnology, Vilnius Phillippe Lambin & Bradly Wouters, University of Maastrich Research Institute Growth and Development (GROW), Maastricht Erik Olai Pettersen, University of Oslo Silvia Pastrorekova, Slovak Academy of Sciences, Bratislava Lorenz Poellinger, Karolinska Institutet, Stockholm Roland Hugo Wenger, University of Zurich Ian James Stratford, The Victoria University of Manchester Peter Ratcliffe & Adrian Harris, Chancellor Masters and Scholars of the University of Oxford, Molecular Oncology Laboratory, Cancer Research UK, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, Oxford Stuart Naylor, Oxford BioMedica Plc, SME Patrick Maxwell, Imperial College of Sciences, London David Blakey, AstraZeneca UK limited, London, IND

Italy Lithuania Netherlands Norway Slovakia Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer Sector

EUROPEAN VASCULAR GENOMICS NETWORKProposal acronym Contract n Duration (starting date) EVGN LSHM-CT-2003-5023254 5 years (01.01.04) EC contribution () Instrument Participants 9.000.000 NoE 28

Abstract:Cardiovascular diseases (CVD) caused 51% of deaths in Europe in 2001, while cancer accounted for 20%. Coronary heart disease and stroke, which result from atherosclerosis, constitute 80% of CVD. Better prevention and treatments have halved age-specific incidence, but the ageing population and adverse trends in obesity and diabetes threaten these improvements. There is also an alarming increase in heart failure, the end stage of coronary heart disease. Future advances depend on developing entirely new strategies. Genomics and proteomics together complete human genome open up fresh horizons for molecular understanding of cardiovascular disease, for identifying new diagnostic measurements and developing new pharmacological, gene and cell-based therapies. The European Vascular Genomics Network (EVGN) seeks to assemble the necessary critical mass and promote multidisciplinary interactions by uniting 25 world-leading basic and clinical institutions from 9 European countries. It focuses on the three areas with greatest therapeutic potential: 1) endothelial dysfunction, an early critical event in atherosclerosis and hence a target for prevention, 2) plaque instability, responsible for precipitating thrombosis and hence most life-threatening acute events, and 3) therapeutic angiogenesis either conventional or cell-based to recover ischaemic organ function and reduce heart failure. Our research armoury spans genomics, proteomics, molecular biology, cell biology, gene transfer and genetic modification in mice, and integrative pathophysiology in man. The EVGN will maximize the scientific and commercial potential of European vascular biology by electronic data-sharing and communication networks, shared research tools, and exchange and training programmes. The EVGN will train tomorrow's lead investigators through a European PhD, which will also address adverse gender balance and encourage excellence in Eastern Europe, which suffers high prevalence of CVD.

Web site:

http://www.evgn.org

Participants:Coordinator France Austria Finland France Germany Israel Italy Dr. Alain Tedgui, Institut National de la Sant et de la Recherche Mdicale tel: +33 1 44 63 18 66 fax: +33 1 42 81 31 28 Alain.Tedgui@larib.inserm.fr Bernd Binder, Department of Vascular Biology, University of Vienna Georg Wick, University of Innsbruck, Medical School, Institute of Pathophysiology, Innsbruck Helga Vetr, Technoclone GmbH, Vienna, SME Seppo Yl-Herttuala, University of Kuopio, A.I. Virtanen Institute, Kuopio Johan Auwerx, Institut Clinique de la Souris, Strasbourg Emmanuelle Benhamou, Inserm-Transfert SA, Paris Ingrid Fleming, Institut fur Kardiovaskulare Physiologie, University of Frankfurt Thomas Mnzel, University Hospital Eppend, Division of Cardiology, Hamburg Georg Nickenig, Medizinische Klinik und Poliklinik, University of Saar, Homburg/Saar Eli Keshet, Faculty of Medicine, Institute of Microbiology, The Hebrew University of Jerusalem Elisabetta Dejana, FIRC Institute of Molecular Oncology, Milan Attilio Maseri, San Raffaele Hospital, Cardiothoracic & Vascular Dept., Milan Federico Bussolino, University of Torino, Dept of Oncological Sciences, Torino Paolo Madeddu, National Institute of Biostructures and Biosystems, Experimental Medicine and Gene Therapy, Osilo Harry Struijker-Boudier, Cardiovascular Research Institute Maastricht (CARIM) Victor van Hingsbergh, Gaubius Laboratory, Leiden Theo van Berkel, University of Leiden, Division of Biopharmaceutics, Leiden Hans Pannekoek, University of Amsterdam, Academic Medical Center, Amsterdam Goran Hansson, Karolinska Hospital, Karolinska Institutet, Stockholm Thomas Lscher, University Hospital, Cardiology, Zrich Francois Mach, University Hospital Geneva, Cardiovascular Biology Research Unit, Geneva Andrew Newby, Bristol Heart Institute, University of Bristol Martin Bennett, Addenbrooke's Hospital, Cardiovascular Medicine, Cambridge Qingbo Xu, St. George's Medical School, Department of Cardiovascular Sciences, London Asif Ahmed, School of Medicine, Reproduction and Vascular Biology, University of Birmingham Patrick Vallance, University College London, Department of Medicine BHF Laboratories, London John Martin, Ark Therapeutics Ltd, London, SME

Netherlands

Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

GENE THERAPY: AN INTEGRATED APPROACH FOR NEOPLASTIC TREATMENTProposal acronym Contract n Duration (starting date) GIANT LSHB-CT-2004-512087 5 Years (01.01.05) EC contribution () Instrument Participants 9.700.000 IP 14

Abstract:Translation of genetic knowledge from the Human Genome into disease-specific therapy for untreatable congenital and acquired diseases is now reality. However, the gene therapy vectors currently used in experimental settings can be developed for safe clinical application only if fundamental problems are solved: ie the limitation of vector dose by attachment targeting and expression control and a decrease of non-specific toxicity. Minimisation of vector immunogenicity (stealthing) is necessary to reduce bloodstream and immune-mediated reduction of effective vector concentration. In the GIANT project, targeting and stealthing of both viral and non-viral vectors will be used to select candidates for testing in Phase I clinical studies. GIANT will concentrate firstly on one uniform model system and disease target (prostate carcinoma) for vector testing standardisation and in vitro, preclinical and clinical vector comparison. We will use a clinically approved vector backbone of adenoviral constructs re-targeted to prostate cancer via surface antigens, and hybrid prostate targeted promoters. The consortium includes a GMP vector production facility and clinical facilities with scientific and ethical permission to carry out human cytotoxic gene therapy trials, guaranteeing the immmediate translation of selected vectors into the clinical testing. The biomaterials obtained will serve to develop new assays for vector distribution, efficacy and monitoring of the immune response against various vector systems. The GIANT participants have a long record of EU-based scientific collaboration and expertise in ethically approved clinical vector generation. The SMEs own international patents on retargeting vectors and target discovery methods, providing a technology platform for further exploration of promising targets and innovative approaches to facilitate treatment of neoplastic diseases. An external Scientific Advisory Board will be convened to oversee progress.

Web site:

http://www.york.ac.uk/depts/biol/units/cru/giant

Participants:Coordinator United Kingdom Czech Republic France Germany Netherlands Sweden United Kingdom Prof. Norman James Maitland, Univ. York, Cancer Research Unit, Department of Biology, York tel: +44 1904 328700 fax: +44 1904 328710 njm9@york.ac.uk Karel Ulbrich, Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic, Department of biomedicinal polymers, Prague Jean-Paul Behr, Universite Louis Pasteur, Faculte de Pharmacie, Laboratoire de Chimie Genetique, UMR 7514, Illkirch Graffenstaden Patrick Erbacher, Polyplus Transfection, Illkirch, SME Stefan Kohchanek, Universitat Ulm, Division of Gene Therapy, Ulm Ernst Wagner, Ludwig-Maximilians-Universitaet Muenchen, Department of Pharmacy, Chair Pharmaceutical Biology - Biotechnology, Munich Chris Bangma, Erasmus MC, University Medical Center, Department of Urology, Rotterdam Rob C Hoeben, Leids Universitair Medisch Centrum, Dep. of Molecular Cell Biology, Leiden Wytske van Weerden, Scuron B.V., Rotterdam, SME Thomas Totterman, Uppsala Universitet, Department of Oncology, Radiology and Clinical Immunology / Division of Clinical Immunology, Uppsala Leif Lindholm, Got-a-Gene AB, Gothenburg, SME Leonard Seymour, The Chancellor, Masters and Scholars of the University of Oxford, Department of Clinical Pharmacology, Oxford Alan Raymond, Pro-Cure Therapeutics L.t.d, York, SME Kerry Fisher, Hybrid Systems Ltd., Oxford, SME

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

DEVELOPMENT AND APPLICATION OF TRANSPOSONS AND SITE-SPECIFIC INTEGRATION TECHNOLOGIES AS NON-VIRAL GENE DELIVERY METHODS FOR EX VIVO GENE-BASED THERAPIESProposal acronym Contract n Duration (starting date) INTHER LSHB-CT-2005-018961 3 years (01.11.05) EC contribution () Instrument Participants 2.800.000 STREP 10

Abstract:Considerable effort has been devoted to the development of gene delivery strategies for the treatment of inherited and aquired disorders in humans. Ex vivo gene therapies are based on removing cells from a patient, introducing a therapeutic gene construct into the cells, and implanting the engineered cells back into the patient. Currently, both viral and non-viral methods are used for gene delivery. Viral vectors are efficient in gene transfer, but their use raises serious safety concerns. Non-viral methods are usually safer but less efficient in providing long-term therapeutic transgene expression. Transposable elements can be considered as natural, non-viral delivery vehicles capable of efficient genomic insertion. In this project, novel gene transfer technologies will be established by developing transposon vectors that mediate efficient and targeted integration of therapeutic genes into the genome. Therapeutic gene constructs will be made in transposon vectors, and delivered into cells ex vivo, using cutting edge non-viral nucleic acid delivery methods. Application of reversible implantation systems (collagen implants, skin biopumps, and encapsulated cells) will be explored. Animal disease models will include copper metabolism diseases, anemia, hypercholesterolemia, bleeding disorders, chronic grnulomatous disease and neurological disorders. Genomic insertion, transgene expression and phenotypic correction will be investigated. Safety issues of transposon vector administration and genomic integration will be addressed. The involvement of three SMEs will mobilise industrial know-how and technology. This project will develop, test and apply new therapeutic tools for somatic gene therapy as an alternative to currently used viral and non-viral technologies, and will have the potential to offer new solutions for diseases that impose significant impairment to citizens? quality of life, as well as burdens on health care services in Europe.

Web site:

not yet

Participants:Coordinator Germany Belgium Denmark Finland Germany Hungary Israel Sweden Dr. Zsuzsanna Izsvak, Max-Delbruck-Centrum fur Molekulare Medizin, Berlin tel: +49 30 9406-2546 fax: +49 30 9406-2547 zizsvak@mdc-berlin.de Marinee (Khim Lay) Chuah, Molecular Cardiovascular Medicine Group, Center for Transgene Technology & Gene Therapy, VIB-University of Leuven, Flanders Interuniversity Institute for Biotechnology, Leuven Lars Wahlberg, Research and Development / Clinical Development, NSGene A/S, Ballerup, SME Thomas Jensen, The Kennedy Institute-National Eye Clinic, The Kennedy Institute-National Eye Clinic, Glostrup Seppo Yla-Herttuala, A.I. Virtanen Institute, Department of Biotechnology and Molecular Medicine, University of Kuopio Herbert Mller-Hartmann, Research & Development, amaxa GmbH, Kln, SME Balazs Sarkadi, Department of Molecular Cell Biology, National Medical Center, Budapest Peter Krajcsi, Solvo Biotechnology Inc., Budapest, Szeged, SME Eithan Galun, Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Hadassah Medical organization, Jerusalem Ulo Langel, Department of Neurochemistry and Neurotoxicology, Stockholms Universitet, Stockholm

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

DEVELOPING A STEM CELL BASED THERAPY TO REPLACE NEPHRONS LOST THROUGH REFLUX NEPHROPATHYProposal acronym Contract n Duration (starting date) KIDSTEM MRTN-CT-2006-036097 4 years (01.09.2006) EC contribution () Instrument Participants 2.463.000 Marie-Curie RTN 6

Abstract:The aim of this project is to design a stem cell-based therapy to prevent end-stage renal disease caused by reflux nephropathy in children. The two main reasons to focus on this condition are that it is the major cause of kidney failure in children and young adults and secondly, the disease typically takes several years to reach end stage, allowing time for therapies to repair damaged kidneys before they become completely non-functional. Recent advances in stem cell science and tissue engineering present an unprecedented opportunity to design a stem cell therapy for this clinical problem. This project will investigate the properties of several different stem cell types (embryonic stem cells, kidney stem cells, amniotic fluid stem cells and mesenchymal stem cells) in order to determine which is most appropriate for the generation of functional kidney tissue. To do this, novel biomaterials will be designed that will provide a substrate both for the generation of kidney progenitor cells and for their transplantation.

Web site:

http://www.kidstem.org

Participants:Coordinator United Kingdom Austria Germany Italy Dr. Patricia Ann Murray, School of Biological Sciences, University of Liverpool, Liverpool tel: +44 151 795 4456 fax: +44 151 794 5517 p.a.murray@liverpool.ac.uk Markus Hengstschlaeger, Medical University of Vienna, Vienna C Werner, Max Bergmann Center of Biomaterials Dresden, Leibniz-Institut fur Polymerforschung Dresden e.V., Dresden Giovanni Gamussi, Department of Internal Medicine, Laboratory of Renal Immunopathology, Universita' Degli Studi di Torino, Turin Giuseppe Remuzzi, Department of Molecular Medicine / Mario Negri Institute for Pharmacological Research, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo Jamie Davies, Centre for Integrative Physiology, University of Edinburgh, Edinburgh

United Kingdom

Commission: Directorate General for Research - Human ressources and Mobility Directorate - Marie Curie Actions

COMBINED ISOLATION AND STABLE NONVIRAL TRANSFECTION OF HEMATOPOIETIC CELLS ? A NOVEL PLATFORM TECHNOLOGY FOR EX VIVO HEMATOPOIETIC STEM CELL GENE THERAPYProposal acronym Contract n Duration (starting date) magselectofection LSHB-CT-2006-019038 4 years (01.05.06) EC contribution () Instrument Participants 2.800.000 STREP 13

Abstract:The feasibility of ex vivo gene therapy in humans has been demonstrated with retrovirally transduced hematopoietic stem cells. At the same time, risks associated with the use of retroviral vectors became apparent. We will establish and validate a novel combination technology for hematopoietic cell isolation and nonviral transfection leading to site-specific genomic integration of transfected nucleic acids. This novel technology will be validated by expert groups in hematopoietic stem cell gene therapy and related basic and clinical research. The technology is going to be exploited and disseminated by the company partners Miltenyi Biotech, OZ Biosciences, MolMed, and Poetic Genetics. A platform technology for nonviral transfection of hematopoietic cells in general and hemaptopoietic stem cells in particular, with optional stable genetic modification, will be established by integrating a clinically approved magnetic cell separation technique (CliniMACS) with magnetically enhanced transfection (Magnetofection). Cell nucleus-targeting vectors will be applied. For selected indications, the technology will be practiced with plasmid constructs that provide site-specific genomic integration, either the phage phiC31 integrase system or, alternatively, a drug-inducible AAV-derived replicase/integrase system. Technology validation includes the analysis of genomic integration sites, transcriptom profiling, characterization of stable and inducible trans-gene expression and evaluation of engraftment and persistence in transgenic animal models using molecular biological tools and magnetic resonance imaging. The therapeutic potential will be examined in a SCID-X mouse model in direct comparison with established retroviral technology. Magselectofection is expected to circumvent problems associated with viral vectors, contribute to health care progress and foster the competitiveness of Europe?s biotechnology industry based on its competitive advantage.

Web site:

http://magselectofection.eu

Participants:Coordinator Germany Austria France Germany Dr. Christian Plank, Institute of Experimental Oncology, Klinikum rechts der Isar der Technischen Universitt Mnchen, Munich , 0049-89-4140-4453, 0049-89-4140-4476, plank@lrz.tum.de tel: +31 71 52 66 639 fax: +31 71 52 48 158 p.c.w.hogendoorn@lumc.nl Peter Steinlein, BioOptics Department, Research Institute of Molecular Pathology, Vienna, IND Olivier Zelphati, R&D, Oz Biosciences, Marseille, SME Joseph Rosenecker, Department of Pediatrics, Ludwig-Maximilians-Universitt, Munich Lena Grimm, Fraunhofer Patentstelle, Fraunhofer Gesellschaft zur Frderung der angewandten Forschung e.V., Munich Ian Johnston, Research and Development, Miltenyi Biotech GmbH, Bergisch Gladbach, IND Tsvee Lapidot, Department of Immunology, Weizmann Institute of Science, Rehovot Fulvio Mavilio, Discovery, Molecular Medicine S.p.A., Milano, SME Marcel Thalen, Synco Bio Partners B.V., Amsterdam, SME Gerard Wagemaker, Hematology, Stem Cell Gene Therapy Development, Erasmus University Medical Center, Rotterdam Zygmunt, Pojda, Department of Experimental Hematology & Cord Blood Bank, M. SklodowskaCurie Memorial Cancer Center and Institute of Oncology, Warsaw Melania Babincova, Department of Nuclear Physics and Biophysics, Comenius University, Bratislava Michele P. Calos, Department of Genetics, Stanford University School of Medicine, Stanford, California, Stanford, California

Israel Italy Netherlands Poland Slovakia United States

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

MODULAR DEVICES FOR ULTRAHIGH-THROUGHPUT AND SMALL VOLUME NUCLEOFECTIONProposal acronym Contract n Duration (starting date) MODEST LSHG-CT-2006-037291 3 years (01.02.07) EC contribution () Instrument Participants 2.755.468 SME-STREP 5

Abstract:Modification of cells is a central topic in pharmaceutical and medical sciences as well as in basic research. Innumerable opportunities, e.g., in discovery of new regulatory pathways, novel targets, and potential drug candidates as well as clarification of signal transduction are addressed by cell transfection technology. The dominant consideration for cell manipulation is the type of cells used. Until now, most often conventional, immortal cell lines, being cultured for years or even decades in flasks, have been assigned to this specified use, although they are mainly irrelevant in physiological and medical repects. The optimal choice would be primary cells, since they are distinctly closer to the physiological situation than cell lines. Researchers would make rapid strides in the analysis of the biology of cells towards the development of therapeutics and new types of treatments as well as possible cures for a variety of diseases and injuries would be facilitated by using primary cells instead of cell lines. However, primary cells until recently were hard or often even impossible to transfect by non-viral methods, and consequently, many researchers still hesitate to adopt these cells despite their unquestionable advantages. With the advent of the nucleofection technology, a unique method for the highly efficient transfection of primary cells was recently made available to the life science community. With MODEST the main objectives are i) the development of devices for one-step, ultra high throughput nucleofection of primary cells in modular multi-well plates, and ii) the application of this technology to the highly relevant area of immunological as well as neuronal disorders to facilitate investigations of possible mechanisms of intervention.

Web site:

not yet

Participants:Coordinator Germany Estonia Germany Sweden Dr., Birgit, Nelsen-Salz, administration, amaxa GmbH, Koeln, DE, undefined, Germany, Y, IND, PRC, +49-221-99199 148, +49-221-99199 119, birgit.nelsen-salz@amaxa.com tel: +31 71 52 66 639 fax: +31 71 52 48 158 p.c.w.hogendoorn@lumc.nl Kaia Palm, Protobios Ltd., Tallinn, SME Alexander Scheffold, Immunomodulation, Deutsches Rheuma Forschungszentrum Berlin, Berlin Jorg Potzsch, RNAx GmbH, Berlin, Thomas Schaumann, Manager Life Science Sales, Teleca Sweden East AB, Stockholm

Commission: Directorate General for Research - Health Directorate - Unit F4 Fundamental Genomics

DEVELOPING MOLECULAR MEDICINES FOR CANCER IN THE POST GENOME ERA BASED ON TELOMERASE AND RELATED TELOMERE-MAINTENANCE MECHANISMS AS TARGETSProposal acronym Contract n Duration (starting date) MOL CANCER MED LSHC-CT-2003-502943 4 years (01.10.04) EC contribution () Instrument Participants 4.000.000 IP 14

Abstract:Cancer is a European public health problem of overwhelming human and economic significance. There is now an improved molecular understanding of the key genetic, biochemical and cellular changes leading to cancer, in significant part due to the efforts of diverse groups of world-class EU-based scientists. With the completion of the human genome sequence imminent, it is now timely to initiate a major European co-ordinated effort to translate fundamental scientific knowledge about cancer into safer, more effective, therapies and improved early diagnostic procedures. The cellular immortality enzyme telomerase (one of the most promising universal cancer markers) and associated telomere maintenance mechanisms, represent novel anti-cancer targets of enormous therapeutic and diagnostic potential. In MOL CANCER MED, we have established a multinational EU translational cancer research consortium, in which talented cancer geneticists and molecular biologists will interact with prominent pharmacologists, clinicians and pathologists to develop these exciting new cellular targets into measurable pre-clinical advances, within a 4-year timeframe. The project has been structured into three, highly interactive Areas of Activity, involving the fundamental evaluation and pre-clinical validation of: (i) telomerase as a target for cancer treatment and diagnosis based on new molecular knowledge about its expression and function, (ii) associated downstream telomere maintenance mechanisms as additional targets for novel drug design, and (iii) new anticancer drugs based on these targets. The Consortium will bring to bear diverse and complementary technological know-how of considerable power to deliver the above primary objectives. Effective management will maximize synergies across MOL CANCER MED in order to produce genuine improvements in the design of new treatments that promise to be active against a broad spectrum of common human malignancies.

Web site:

http://www.brunel.ac.uk/about/acad/health/healthres/researchareas/bicgp/molcancermed

Participants:Coordinator United Kingdom Denmark France Germany Italy Spain Sweden Switzerland United Kingdom Prof. Robert F Newbold, Brunel Institute of Cancer Genetics and Pharmacogenomics tel: +44 1895 203090 fax: +44 1895 274348 rnewbold@atlas.co.uk Nedime Serakinci, University of Aarhus Jean-Louis Mergny, Museum National dHistoire Naturelle, INSERM U-565, Paris Uwe Martens, University Hospital, Freiburg Petra Boukamp, DKFZ, Heidelberg Nadia Zaffaroni, National Cancer Institute, Milan Maurizio DIncalci, Instituto Mario Negri, Milan Mara A. Blasco, Spanish National Cancer Centre, Madrid

Gran Roos, Ume University, Ume Joachim Lingner, ISREC, Lausanne W. Nicol Keith, University of Glasgow, Cancer Research UK Beatson Laboratories, Glasgow Stephen Neidle, The School of Pharmacy, University of London, London Eric Kenneth Parkinson, University of Glasgow, School of Veterinary Pathology John Mann, Queens University, Belfast

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer Sector

AMPLIFICATION OF HUMAN MYOGENIC STEM CELLS IN CLINICAL CONDITIONSProposal acronym Contract n Duration (starting date) MYOAMP LSHB-CT-2006-037479 3 years (01.12.06) EC contribution () Instrument Participants 2.480.000 SME-STREP 10

Abstract:The aim of this network is to synergize expertises from European basic researchers, leaders in their field, and European SMEs specialized in stem cell amplification and in safety of these procedures, to set up conditions for autologous transfer of human stem cells in GMP conditions for the treatment of DMD by exon-skipping. Cell therapy trials in DMD has never fulfilled the promises raised by the early results obtained in mouse models. Several groups have recently demonstrated the possibility of generating a truncated, but functional dystrophin using exon-skipping, by masking splicing sequences with oligonucleotides introduced by either direct or viral transfer. The direct approach can be used as many times as needed, but is extremely expensive, while the AAV approach allows a large dissemination of the masking sequences, but triggers an immune response to the vector, and therefore can be used only once. Cell therapy can thus be used to target sites which have not been cured by the AAV approach, using autologous cells as vectors which, by fusing with the regenerating fibres of the patient, will bring a functional dystrophin to these fibres. Myoblasts become progressively exhausted in DMD patients as the disease progresses, while stem cells, such as mesoangioblasts or AC133+, remain intact and functional. However, little is known either about the possibility to transduce these cells with oligonucleotides or vectors for exon-skipping, or the methods that can be used to expand these cells in GMP conditions. The technical and ethical guidelines resulting from this network will enable SMEs to expand stem cells with myogenic potential in GMP conditions for clinical trials in patients with DMD or other neuromuscular diseases. This network is a natural link between MYORES, an existing NoE dedicated to muscle research, and TREAT, an upcoming NoE dedicated to therapeutics (FP6 4th Call, line LSH-2005-2.1.1-7), since it gathers specialists belonging to both NoE.

Web site:

not yet

Participants:Coordinator France France Dr. Gillian Butler-Browne, Stem cell and muscle biology, Institut National de la Sant et de la Recherche Mdicale, Paris tel: +33 1 40 77 96 36 fax: +33 1 53 60 08 02 butlerb@ext.jussieu.fr Anton Ottavi, European project management department, Inserm-transfert, St Beauzire, Paris Otto Merten, Dpartement de Dveloppement, Genethon, Evry, SME Christophe Gaillard, GenoSafe SAS, Evry Luis Garcia, Centre de recherche et d'applications sur les thrapies gniques, Centre National de la Recherche Scientifique, Evry Felicia M Rosenthal, Cellgenix technologie Transfer GmbH, Freiburg, SME Yvan Torrente, Dipartimento di scienze neurologiche, Universit degli Studi di Milano, Milano Giulio Cossu, Stem Cell Research Institute, DIBIT, Fondazione Centro San Raffaele del Monte Tabor, Milan Mallen Huang, 3H Biomedical AB, 3H Biomedical AB, Uppsala, SME Jennifer E Morgan, Department of Pediatrics, Division of Medicine, Imperial college London, The Dubowitz Neuromucular Unit, Hammersmith Hospital, Imperial College of Science, Technology and Medicine, London

Germany Italy Sweden United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

MOLECULAR MECHANISMS OF NEURONAL DEGENERATION: FROM CELL BIOLOGY TO THE CLINICProposal acronym Contract n Duration (starting date) NEURONE LSHM-CT-2004-512039 4 Years (01.01.05) EC contribution () Instrument Participants 8.300.000 NoE 29

Abstract:NeuroNE is Europes premiere research network for the creation of novel therapeutic approaches to neurodegenerative disease and neurotrauma, which represent an urgent socio-economic and human need. The NeuroNE consortium (22 academic groups, 5 SMEs and 1 management partner in 9 different countries) is taking a multi-disciplinary (functional genomics and proteomics, physiology, chemistry, clinical studies) and multi-faceted (disease mechanisms, biology of cell death and survival, regeneration mechanisms, high-throughput screening, gene- and cell-based therapies) approach to this problem. Among the neurodegenerative diseases, the network is focussing on Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Spinal cord injury (SCI) will be the main model for neurotrauma. NeuroNE brings together investigators from different backgrounds (basic scientists, active clinicians and therapeutically-oriented SMEs) to work at all levels on the target diseases using the methods of postgenomic science, molecular and cell biology, animal models, therapeutic strategies and clinical studies. Professional project management provides efficient integration, realization of scientific objectives and knowledge management. The scientific infrastructure of the network includes shared NeuroNE-funded core facilities in 7 centres. The network has employed a team of scientists based in the participating laboratories who will conduct research and form collaborations amongst the different participants. The network has a program of scientific meetings that will consist of three major international plenary meetings and ten scientific workshops on specific topics. To feed back the benefits of integration into EU society, the network is working with patient organizations, identified associated research groups who will benefit immediately from our infrastructures, and has opened network meetings to identified scientists from emerging research centres.

Web site:

http://www.euneurone.net

Participants:Coordinator United Kingdom Belgium France Prof. James Fawcett, UNICAM, Cambridge University Centre for Brain Repair, Cambridge tel: +44 1223 33 11 88 fax: +44 1223 33 11 74 jf108@cam.ac.uk Bart De Strooper, Flanders Interuniv. Inst. Biotechnology VZW, Depart. Human Genetics, Leuven Nicole Deglon, URA CEA CNRS 2210 & ImaGene Program, Service Hosp. Frederic Joliot, Orsay Brigitte Pettmann, Institut Nationale de la Sante et de la Recherche Medicale, UMR 623, Marseille Jonathan Dando, Inserm Transfert Sa, European Project Management Department, Paris Rebecca Pruss, Trophos SA, Marseille, SME Jean-Chretien Norreel, Pharmaxon, R&D, Marseille, SME Harold Cremer, Centre Nationale de la Recherche Scientifique, IBDM, Marseille Hilmar Bading, Ruprecht-Karls-Universitaet Heidelberg, Institute of Neurobiology, Heidelberg Mathias Baehr, UKG-GOE, Center for Neurological Medicine, Depart. Neurology, Goettingen Christian Haass, Universitaet Muenchen, Adolf-Butenandt-Inst of Biochemistry, Munich Rudiger Klein, Max-Planck-lnstitute of Neurobiology, Depart. Mol. Neurobiology, Martinsried Bernhard Landwehrmeyer, Universitaetsklinikum Ulm, Department of Neurology, Ulm Angelika Bonin-Debs, Xantos Biomedicine AG, R&D, Munchen, SME Andreas Bosio, Memorec Biotec GmbH, Cologne, IND Aaron Ciechanover, Technion - Israel Institute of Technology, Department of Biochemistry, Faculty of Medicine, Haifa Ernesto Carafoli, Istituto Veneto di Medicina Molecolare, Padova Elena Cattaneo, Universita degli Studi di Milano, Dipartimento di Scienze Farmacologiche, Milano Pier-giorgio Strata, Rita Levi Montalcini Center for Brain Repair, Dipart. di Neuroscienze, Turin Jose Ramon Naranjo Orovio, Consejo Superior de Investigaciones Cientificas, Centro Nacional de Biotecnologia, Depto. Molec. Cell. Biol. , Madrid Cristina Garmendia, Genetrix S.L, Tres Cantos, Madrid, SME Patrik Brundin & Anders Bjorklund, Lunds Universitet, Wallenberg Neuroscience Center, Faculty of Medecine, Lund Carlos Ibanez, Karolinska Institutet, Depart. Neuroscience, Div. Mol. Neurobiology, Stockholm Patrick Aebischer, Swiss Federal Inst. Technology, Inst. Neurosciences, Lausanne Pico Caroni, Zweigniederlassung Friedrich Miescher Institute Biomedical Research (FMI), Basel Ann Kato, University Geneva, Dept. Neuroscience, Faculty of Medicine, Geneva Martin Schwab, University Zurich, Neurowissenschaften, Zurich Nigel Leigh, Kings College London, Depart. of Neurology, Institute of Psychiatry, London

Germany

Israel Italy Spain Sweden Switzerland

United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

THE DISCOVERY OF FUTURE NEURO-THERAPEUTIC MOLECULESProposal acronym Contract n Duration (starting date) NEUROscreen LSHB-CT-2006-037766 3 years (01.01.06) EC contribution () Instrument Participants 2.050.000 STREP 9

Abstract:NEUROscreen is an industry-lead project combining novel neural stem cell bioassays & post-genomic chemical genetics to discover potential drugs of relevance to neurological diseases, regenerative medicine & cancer. Small molecule inhibitors of the growth of clonal, human neural cancer stem cells have the prospect of being unique medicines targeting the elusive cancer stem cell. Chemical modulators augmenting the growth, survival or differentiation of normal brain cells have a prospect as preventative or regenerative medicines for neurodegenerative diseases i.e. Alzheimer's, stroke & Huntingtons disease. The consortium will use quality controlled cell lines & genetic engineering technology to design unique bioassays with which the biological modulating capacity of small molecules will be evaluated in a multi-replicate manner. Advanced chemistry will be used for the intuitive design and synthesize of biologically active molecules. Screening will be achieved with cells made to a quality & quantity via innovative bioprocesses & handled with state of the art robotics. The project will enhance the utility of the cell lines by delimiting the in vitro neural potency of the stem cells; ongoing determination of differentiation capacity serves as a rigorous confirmation of utility. The project will focus on specific activities germane to a wider applied research field than its seeding project EuroStemCell. The consortium & project have been designed with a crucial alignment in mind to objectives of the Work Programme/Specific Programme for Integrating & strengthening the ERA i.e. gender & innovation aspects in research, international cooperation (3 countries & a new member state) and fostering ethical awareness in research involving human stem cells. More than 50% of partners represent European small- & medium-sized companies and this balance structures a consortium with greater potential than individual parts & will directly strengthen the ERA foundations.

Web site:

not yet

Participants:Coordinator Germany Germany Italy Dr. Timothy Allsopp, Stem Cell Sciences UK Ltd, Edinburgh, SME tel: +44 131 650 5850 fax: +44 131 662 9779 tim.allsopp@stemcellsciences.com Stefanie Terstegge, Cellomics Platform, Robotics department, Life & Brain GmbH, Bonn, SME Oliver Brstle, Institute of Reconstructive Neurobiology, Rheinische Friedrich Wilhelms Universitt Bonn, Bonn Dorotea, Rigamonti, Dialectica srl, Milan Pasquale De Blasio, BioRep SrL, Milan Luciano Conti, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, Universit degli Studi di Milano, Milan Austin Smith, Institute for Stem Cell Biology, The Chancellor, Master and Scholars of the University of Cambridge, Cambridge Franois Guillemot, Division of Molecular Neurobiology, National Institute for Medical Research, Medical Research Council, London

United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

NERVOUS SYSTEM REPAIRProposal acronym Contract n Duration (starting date) NSR MRTN-CT-2004-504636 4 years (01.01.2004) EC contribution () Instrument Participants 2.600.335 Marie-Curie RTN 8

Abstract:Diseases and injuries that affect central nervous system neurons are among the illnesses that are hardest to cure. Their frequency increases dramatically with the ageing of the EU population. The complexity of these illnesses and the hightech nature of planned therapeutics makes research in this field discouragingly expensive for the pharmaceutical industry and SME investors. European funding will allow us to bring into play almost the complete range of techniques that are currently applied to the nervous system. Clinicians, industrial partners and patient groups are also involved and will contribute both to the training and to the orientation of this joint Programme. Results generated by this network are likely to have significant effects on future therapies of patient affected by neurotrauma and neurodegenerative diseases. Our overall strategy is to use new scientific findings to further advance the technologies of brain repair to the point where they can be considered as viable clinical strategies. The main technological approaches can be applied across the range of damaging conditions of the central nervous system (CNS). They are: Stem cell/cell therapy, Protection/trophic factors, Gene therapy, regeneration/plasticity. Backing these up are enabling technologies: proteomics, genomics/post genomics, drug discovery, clinical protocols/preliminary trials, imaging, animal models.

Web site:

http://www.euneuro.net/project

Participants:Coordinator France Germany Italy Switzerland Sweden United Kingdom Dr. Christopher Henderson, Developmental Biology Institute of Marseille (IBDM), Marseille tel: +33 491 26 97 60 fax: +33 491 26 97 57 chris@ibdm.univ-mrs.fr Mathias Bhr, Gttingen University Neurological Clinic, Gttingen Rdiger Klein, Max Planck Institute of Neurobiology, Martinsried Piergiorgio Strata, University of Turin, Department of Neuroscience, Turin Patrick Aebischer, Swiss Federal Institute of Technology (EPFL), Lausanne Patrik Brundin, Wallenberg Neuroscience Center, Lund Carlos Ibez, Karolinska Institute, Stockholm James Fawcett, Cambridge University Centre for Brain Repair, Cambridge

Commission: Directorate General for Research - Human ressources and Mobility Directorate - Marie Curie Actions

BONE FROM BLOOD: OPTIMISED ISOLATION, CHARACTERISATION AND OSTEOGENIC INDUCTION OF MESENCHYMAL STEM CELLS FROM UMBILICAL CORD BLOODProposal acronym Contract n Duration (starting date) OsteoCord LSHB-CT-2006-018999 3 years (01.01.2006) EC contribution () Instrument Participants 2.486.000 STREP 9

Abstract:There is an urgent clinical requirement for appropriate bone substitutes that are able to replace current autologous and allogeneic grafting procedures for the repair of diseased or damaged skeletal tissues. Mesenchymal stem cells (MSCs), found predominantly in the bone marrow, are able to differentiate into osteogenic, chondrogenic, adipogenic and tenogenic lineages, thus offering considerable therapeutic potential for tissue engineering applications. However, invasive extraction procedures and insufficient viable cell yields have necessitated the identification of alternative tissue sources of MSCs. Growing evidence suggests that umbilical cord blood (UCB) contains a population of rare MSCs that are able to undergo multilineage differentiation. The aim of this proposal is optimise the isolation and expansion of MSCs from human UCB (CB-MSCs). The differentiation capacity of CB-MSCs will be examined, with a specific focus on osteogenesis. The CB-MSCs will be characterised by genomic, proteomic and bioimpedance profiling, pre- and post-osteogenic differentiation, and compared to MSCs isolated from human bone marrow as well as embryonic stem cells. Full bioinformatics integration of datasets will identify specific and/or novel signalling factors associated with CB-MSCs. The immunophenotype and alloreactivity of CB-MSCs will be determined. Comparative analyses of the population doubling times, telomere length and telomerase activity will identify the lifespan of CB-MSCs. Novel expansion techniques will be combined with scale-up procedures and the generation of CB-MSC lines for banking using optimised cryopreservation protocols. In vitro and in vivo biocompatibility assays using a range of biomimetic scaffolds will be exploited, complementing in vivo homing and engraftment models. Our integrated approach using complementary expertise will provide a timely and thorough evaluation of CB-MSCs and define appropriate routes for their therapeutic implementation.

Web site:

http://www.bonefromblood.org

Participants:Coordinator United Kingdom Denmark Germany Dr. Paul Genever, Biology, University of York tel: +44 1904-328649 fax: +44 1904-328659 pg5@york.ac.uk Moustapha Kassem, Department of Endocrinology, University Hospital of Odense, Odense Jens Andersen, Center for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense Hagen Thielecke, Biohybrid Systems Department, Fraunhofer Institute for Biomedical Engineering, St. Ingbert, Mnchen Hermann Eichler, Institute of Transfusion Medicine & Immunology, Stem Cell Laboratory, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim Yaron Daniely, Gamida-Cell, Ltd. Cell Therapy Technologies, Jerusalem, SME Helder Cruz, ECBio Investigao e Desenvolvimento em Biotecnologia S.A., Oeiras, SME Lee D.K. Buttery, Tissue Engineering Group, School of Pharmacy, University of Nottingham Robin Andrew Quirk, Regentec Ltd, Nottingham, SME

Israel Portugal United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

GENE THERAPY FOR EPIDERMOLYSIS BULLOSA: A MODEL SYSTEM FOR TREATMENT OF INHERITED SKIN DISEASESProposal acronym Contract n Duration (starting date) SKINTHERAPY LSHB-CT-2005-512073 3 years (15.04.05) EC contribution () Instrument Participants 2.079.900 STREP 8

Abstract:The project aims to develop a gene therapy technology model based on autologous transplantation of skin made in vitro from genetically modified epidermal stem cells. This includes developing vectors, gene transfer technology, and preclinical models of gene therapy of rare inherited defects treatable with sustained local delivery of a recombinant protein. The research focuses on dystrophic epidermolysis bullosa (DEB), a rare, disabling skin disease caused by inherited defects of collagen type VII. The workplan consists in: - Recruiting, genotyping and characterizing at molecular level cohorts of patients with recessive and dominant DEB - Isolating epithelial stem cells from the skin of DEB patients and DEB dogs, a spontaneous large animal model for the disease - Developing viral vectors (oncoretroviral, lentiviral, and hybrid adeno/AAV vectors) to integrate and stably express the collagen VII cDNA in DEB epidermal stem cells ex vivo Transducing highly clonogenic DEB keratinocytes with the most appropriate vector(s) - constructing skin equivalents made with genetically corrected DEB cells to assess the full morphological and functional reversion of the DEB phenotype - Constructing transplantable epithelia using genetically corrected DEB cells and preclinical assessment of their performance in vivo in appropriate immune competent animal models - Developing a technology for production and downstream processing of clinical-grade viral vectors preparations under GMP/GLP standards - Establishing SOP, protocols and guidelines to genetically modify epidermal stem cells used to produce skin implants for clinical use Disseminating results. The projects immediate goal is to develop a gene therapy approach to DEB and design appropriate phase I/II clinical trials to exploit the knowledge generated. This research ultimately targets the implementation of a technology applicable to other genetic protein deficiencies requiring local or systemic delivery of active molecules.

Web site:

http://www.debra-international.org/researche1.htm

Participants:Coordinator France France Germany Italy Spain United Kingdom Prof. Guerrino Meneguzzi, Institut National de la Sant et de la Recherche Mdicale, Nice tel: +33 4 93 37 77 79 fax: +33 4 93 81 14 04 meneguzz@unice.fr Jonathan Dando, INSERM Transfert SA, Paris Leena Bruckner-Tuderman, Universitaetsklinik Freiburg Michele De Luca, Fondazione Banca Degli Occhi del Veneto O.N.L.U.S., Venezia-Mestre Fluvio Mavilio, Universita' di Modena e Reggio Emilia, Modena Anna Stornaiuolo, Molecular Medicine S.p.A, Milan, SME Jose Luis Jorcano Noval, Centro de Investigaciones Energeticas Medioambientales y Tecnologicas, Madrid John Richard William Dart, DEBRA Europe, Crowthorne

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

EMBRYONIC STEM CELLS FOR THERAPY AND EXPLORATION OF MECHANISMS IN HUNTINGTON DISEASEProposal acronym Contract n Duration (starting date) STEM-HD LSHB-CT-2006-037349 3 years (01.12.06) EC contribution () Instrument Participants 2500.000 STREP 8

Abstract:Embryonic stem cell (ES) lines have potential interest for exploring mechanisms and therapeutics of geneticallydetermined diseases, due to their fundamental attributes, unlimited expansion and pluripotency: isogenic cells of any phenotype can be produced in any requested amount. STEM-HD aims at validating this potential for Huntington's disease (HD), on the basis of the analysis of ES cell lines expressing the mutant HD gene. These will be obtained either following derivation after pre-implantation genetic diagnosis from an embryo expressing the mutant huntingtin gene (existing cell line) or through engineering of existing native human and mouse ES cell lines. The consortium will: - establish protocols to enrich ES cell progeny in cell phenotypes of interest, in particular striatal GABA neurons. - design and implement infrastructures for mass cell production and long-term cultures of ES cells either undifferentiated or following guided differentiation. - identify, using large-scale "resource-driven" approaches, HD biomarkers in mutant HD-expressing ES cells progeny appearing as alteration in the expression of genes (transcriptome). Mutant-association of these molecular markers will be validated using patients samples and assays developed. - explore the mechanisms of the diseases in the mutant HD-expressing ES cells progeny using functional genomics (RNAi and gene overexpression) and "hypothesis-driven" approaches. - perform high content drug screening on HD gene-carrying ES cell progeny using validated biomarkers as signals and available compounds libraries.

Web site:

not yet

Participants:Coordinator France Belgium France Israel Italy United Kingdom Dr. Marc Peschanski, Unit 421-ISTEM, Institut National de la Sant et de la Recherche Mdicale, Evry tel: +33 169471150 fax: +33 169471153 mpeschanski@istem.genethon.fr Karen Dora Sermon, Research Group Reproduction and Genetics, Vrije Universiteit Brussel, Brussels Jacques Haiech, Institut Gilbert Laustriat UMR CNRS 7175, University Strasbourg / Louis Pasteur, Illkirch Abderrahim Mahfoudi, European Projects Management Department, Inserm Transfert, Paris Joseph Itskovitz-Eldor, Department of Obstetrics and Gynecology, Rambam Medical Center, Technion - Israel Institute of Technology, Haifa Dorotea Rigamonti, Dialectica srl, Milano, SME Elena Cattaneo, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, Universit degli Studi di Milano, Milan Nicholas Allen, School of Biosciences, Cardiff University, Cardiff

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

PRE-CLINICAL EVALUATION OF STEM CELL THERAPY IN STROKEProposal acronym Contract n Duration (starting date) STEMS LSHB-CT-2006-037328 3 years (01.12.06) EC contribution () Instrument Participants 2.400.000 STREP 9

Abstract:Using stem cells (SC) multipotent properties has become a challenging research field for most clinical areas, especially in disciplines lacking treatment options such as brain disorders and lesions. In particular, stroke or ischemic cerebrovascular disease accounts for roughly half of the patients hospitalised for neurological diseases and is associated with a large proportion of the health care costs in Europe. Until now, all neuroprotective approaches having yielded positive results in animal models have proven ineffective in clinical trials. SC clonal populations expected capacity to self-renew and differentiate efficiently into the desired cell type promise to produce beneficial effects in many diseases. Several studies indicate the therapeutic potential of SC in stroke after transplantation of various SC types. However, standardisation of conditions to regulate SC proliferation and differentiation to produce the ideal graft need to be better defined; changes induced by their transplantation into lesioned brain structures are unknown, as is the full extent of functional improvement at long-term post-stroke delays. STEMS deals with the therapeutic aim of using SC to reduce stroke-induced brain dysfunctions. Its main objective is to determine the extent and limits of SC therapy in stroke to pave the way for clinical trials. It will be achieved through the completion of six successive and complementary goals: - Definition of standard experimental conditions for proliferation, guided differentiation and mass-production - Identification of the best transplantation protocol regarding post-stroke delays in a rat model of focal ischemia - Control of safety and compatibility aspects - Quantification of the effects of SC transplantation on functional impairments - Transposition of the optimal experimental conditions to non-human primates - Definition of the relevant human cell therapy product and operating procedures to be applied to stroke patient

Web site:

not yet

Participants:Coordinator France Denmark France Germany Sweden Dr. Brigitte Onteniente, INSERM UMR 421, Institut National de la Recherche Mdicale, Crteil tel: +33 01 49 81 36 72 fax: +33 01 4981 3709 ontenien@im3.inserm.fr Vagn Holmegaard, Medical Biotechnology Center, The University of Southern Denmark, Odense Philippe Hantraye, URA CEA CNRS 2210, Service Hospitalier Frdric Joliot, Commissariat l'Energie Atomique, Orsay Karine Baudin, European Project Management Department, INSERM-Transfert, Paris Klaus G. Reymann, Projet Group Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg Patrik Brundin, Department of Experimental Medical Science/Medical Faculty/Division of Neuroscience/Neuronal Survival Unit, Lunds Universitet, Lund Jonas Frisn, Department of Developmental Biology/Cell and Molecular Biology Program/Frisn Group, Karolinska Institutet, Stockholm Johan Hyllner, Cellartis AB, Gteborg, SME

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

REDUCING ANIMAL EXPERIMENTATION IN PRECLINICAL PREDICTIVE DRUG TESTING BY HUMAN HEPATIC IN VITRO MODELS DERIVED FROM EMBRYONIC STEM CELLSProposal acronym Contract n Duration (starting date) SyntheGeneDelivery LSHB-CT-2005-018716 3 years (01.12.05) EC contribution () Instrument Participants 2.400.000 STREP 6

Abstract:Our aim is to develop SyntheGeneTransfer (SGT), a new ex-vivo gene delivery protocol to provide stable long-term expression of integrated transgenes. Our clinical objective is to provide gene therapy solutions for some genetic diseases of the neuromuscular and skeletal systems as well as circulating-polypeptide deficiencies that together afflict over 35,000,000 patients in Europe. We have therefore selected mesenchymal and muscle stem cells as model systems in which to develop the SGT protocol.The SGT protocol is designed to overcome three key barriers: transgene internalization in stem cells, transport across the nuclear membrane and integration at a predefined ?safe? genomic locus that will permit transgene expression. To achieve these goals and fully develop the technology, this application draws together a multi-disciplinary European team from four public laboratories and two SMEs. To overcome serious problems with current transfection methods, the teams will develop protocols for internalization and nuclear membrane transport based on Lipoplex, block copolymers and Bioplex. To overcome serious problems with current integration systems, a new targeted transposition system will be developed using a Mos1 mariner transposon.Our main technical objective is to engineer SGT to provide a method for the integration of large transgenes that will be both highly efficient and maintain a stringent level of safety by preventing the oncogenic transformation of the target cells. Optimization of the cellular internalization and nuclear import steps will allow the cells to be treated with a minimal amount of the transgene. This will minimize the probability of illegitimate integration events at unexpected genomic loci. To optimize the integration step of the process, the Mos1 transposon will be engineered to allow targeting to specific loci. The system will also be engineered to accept large transgenes without the concomitant loss of efficiency observed with existing systems.

Web site:

not yet

Participants:Coordinator France France Sweden United Kingdom Dr. Yves Bigot, Etude des Parasites Gntiques - EA3868, Universit Franois Rabelais, Tours tel: +33 247367035 fax: +33 0247367035 bigot@univ-tours.fr ybigot@wanadoo.fr Bruno Pitard, In Cell Art, Nantes, SME Elisabeth Trnquist, Avaris AB, Solna, SME C.I. Edvard Smith, Clinical Research Center, Karolinska Institutet, Stockholm Ronald Chalmers, Department of Biochemistry, University of Oxford Dominic Wells, Laboratory: Gene Targeting Unit, Division of Neuroscience, Technology and Medicine, Faculty of Medecine, Imperial College of Science, Technology and Medicine, London

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

DEVELOPMENT AND PRECLINICAL TESTING OF CORD BLOOD-DERIVED CELL THERAPY PRODUCTSProposal acronym Contract n Duration (starting date) TherCord LSHB-CT-2006-018817 3 years (01.05.2006) EC contribution () Instrument Participants 1.800.000 STREP 9

Abstract:Cord blood is a widely recognized source of hematopoietic progenitor cells for human transplantation in pediatric and, to a lesser extent, also adult patients affected by different hematological disorders. The therapeutic perspectives of cord blood has been recently widened by the discovery that it contains pluripotent stem cells, capable to give rise, in vitro and in vivo, to other than hematopoietic cells. The present project is aimed at investigating the potential of cord blood stem cells for differentiation and tissue repair, with the final goal to develop novel technologies for pre-clinical testing of cord bloodderived cell therapy products. Therefore, the main part of this project will be dedicated to set up and validate innovative technologies for the isolation, amplification and differentiation of pluripotent cells from cord blood, including immunological assays for the evaluation of their immunoreactivity and animal models of human diseases to test their safety and efficacy. Moreover, the presence of a SME in the Consortium is specifically aimed at translate the results obtained from the basic science into GMP procedures to be used in phase I/II clinical protocols.

Web site:

under construction

Participants:Coordinator Italy Germany Israel Italy Dr Lorenza Lazzari, Centro Trasfusionale e di Immunologia dei Trapianti, Ospedale Maggiore Policlinico di Milano IRCCS, Milan tel: +39 255034053 fax: +39 25458129 ctitricerche@policlinico.mi.it Anna Magdalene Wobus, Cytogenetics Department, Research Group: In Vitro Differentiation, Institut fr Pflanzengenetik und Kulturpflanzenforschung, Gatersleben Yaron Daniely, Alliance Manager & Research Team Leader, Gamida-Cell Ltd. Cell Therapy Technologies, Jerusalem, SME Maurizio Pesce, Laboratorio di Biologia Vascolare e Terapia Genica, Centro Cardiologico Monzino, Milan Rita Maccario, Divisione di Oncoematologia Pediatrica, Laboratorio di Ricerca Area Trapianti, Immunologia dei Trapianti, IRCCS Policlinico San Matteo di Pavia, Pavia Willem E. Fibbe, Department of Hematology, Leiden University Medical Center, Leiden Joan Garcia, Barcelona CBB, Barcelona Cord Blood Bank (BCB) Centre de Transfusio I Banc De Teixits - Serveis de Referencia de Catalunya, Barcelona Dominique Bonnet, Haematopoeitic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London Marcela Contreras, National Directorate of Diagnostics, Development & Research - National Blood Service, London

Netherlands Spain United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

MODULATION OF THE RECRUITMENT OF VESSELS AND IMMUNE CELLS BY MALIGNANT TUMORS: TARGETING OF TUMOR VESSELS AND TRIGGERING OF ANTI-TUMOR DEFENSE MECHANISMSProposal acronym Contract n Duration (starting date) TUMOR-HOST GENOMICS LSHC-CT-2005-518198 3 Years (01.11.05) EC contribution () Instrument Participants 2.700.000 STREP 3

Abstract:In addition to oncogenic mutations that act cell-autonomously, tumor cell growth depends on interactions with its microenvironment. Tumor microenvironment consists of cells of hematopoietic and mesenchymal origin, including inflammatory cells, stem and progenitor cells, fibroblasts, endothelial cells and vascular mural cells. Tumor cell growth is known to depend on the interaction of tumor cells with such stromal cells. For example, growing tumor needs to recruit normal endothelial and vascular mural cells to form its blood vessels. In addition, tumor cells induce stromal cells to secrete factors that contribute to tumor cell growth and invasion. Stromal cell -dependent interactions represent an attractive target for cancer therapy, because normal cells are genetically stable, and would not be expected to develop resistance to therapeutic agents. The development of such therapies is hampered by the fact that the molecular mechanisms behind tumor-stroma interactions are often poorly understood. In summary, the workplan entails development of novel advanced functional genomics instruments, technologies and methods for methods to study tumor-host interactions in cancer, and to apply these techniques to the identification of molecules and processes in normal cells which could be targeted by novel anti-cancer therapeutic agents. In addition, we will develop targeted lentiviruses which would allow in vivo delivery of therapeutic agents into tumors. Functional validation of the discovered targets and developed delivery systems will be performed in vivo models of murine tumor growth and dissemination. The work has significant exploitation potential, and applications for health in the understanding of the molecular mechanisms of tumor-host interactions, and in the treatment of cancer.

Web site:

none

Participants:Coordinator Finland Italy Netherlands Dr. Petri Salven, Faculty of Medicine, Developmental and Reproductive Biology Research Program, Helsingin yliopisto, University of Helsinki, Helsinki tel: +35 8919125384 fax: +35 8919125664 petri.salven@helsinki.fi Luigi Naldini, Angiogenesis and Tumor Targeting Research Unit, Fondazione Centro San Raffaele del Monte Tabor, Milan Peter ten Dijke, Division of Cellular Biochemistry, Antoni van Leewenhoek Hospital, The Netherlands Cancer Institute, Leiden

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

X-LINKED ADRENOLEUKODYSTROPHY (X-ALD): PATHOGENESIS, ANIMAL MODELS AND THERAPYProposal acronym Contract n Duration (starting date) X-ALD LSHM-CT-2004-502987 3 years (01.01.04) EC contribution () Instrument Participants 1.800.000 STREP 6

Abstract:Our ultimate goal is to develop new therapies for X-linked adrenoleukodystrophy (X-ALD), the most frequent inherited monogenic demyelinating disease of the central nervous system (1:18,000). X-ALD is characterised by extensive phenotypic variability, which is not correlated to ALD genotype, and leads to death in boys due to cerebral demyelination and to motor disability in adults due to spinal cord degeneration. Allogenic bone marrow transplantation, proven to be beneficial in X-ALD, can be applied only to a limited number of X-ALD patients. Thus, there is no treatment for the majority of patients, in particular those with the severe cerebral form of X-ALD and adults with adrenomyeloneuropathy (AMN). Understanding of the pathogenesis is necessary for the development of novel therapeutic strategies. The still unresolved transporter function of the ALD protein will be studied in reconstituted liposomes. To get further insight into the pathogenesis of X-ALD, we aim to identify genes and proteins that are differentially regulated in the target tissues of patients with cerebral ALD and AMN using Affymetrix analysis of differential mRNA expression and a proteomics approach based on MALDI-TOF mass spectrometry. Additional genome-wide approaches such as mapping of quantitative trait loci will be applied to identify modifier genes that may contribute to the phenotypic variability of X-ALD. We will generate new mouse models that represent a wider phenotypic spectrum of the disease for a more efficient evaluation of therapeutic strategies. Furthermore, we will evaluate four promising new therapy strategies: ALD gene transfer into haematopoietic stem cells, into mesenchymal stem cells, and by direct injection of viral vectors, and pharmacological induction of a related gene as a substitute for the deficient ALD gene. Only the joint effort of the highly qualified partners of this proposal will allow achieving our ambitious aims.

Web site:

none

Participants:Coordinator Austria France Germany Netherlands Prof. Dr. Johannes Berger, Brain Research Institute, University of Vienna tel: +43 1 42 77 62 812 fax: +43 1 4277 9628 Johannes.berger@univie.ac.at Patrick Aubourg, Institut national de la sant et de la recherche mdicale, Paris Jean-Michel Mandel, Human Molecular Genetics Group, IGBMC, Strasbourg Peter Geigle, CellMed AG, Alzenau, SME Klaus-Armin Nava, Max-Plank-Institute of Experimental Medicine, Gttingen Ronald Wanders, Academic Medical Center, Dept. Clinical Chemistry, Paedriatrics & Neurology, University of Amsterdam

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

BUILDING Tissue engineering

47

THIRD GENERATION SCAFFOLDS FOR TISSUE ENGINEERING & REGENERATIVE MEDICINEProposal acronym Contract n Duration (starting date) 3G-SCAFF NMP3-CT-2005-013602 3 years (01.03.05) EC contribution () Instrument Participants 1.699.998 STREP 7

Abstract:We propose to use cells as micro-factories to produce and assemble the molecular components at the nanometer level which is not possible by conventional mechanical engineering. This cellular engineering will be used to produce the supportive structure with desired shape, compliance and mechanical strength at meso- and macroscale levels. We achieve this by engineering cells to express the desired components creating bioartificial scaffolds which mimick the natural extracellular matrix and will fulfil the requirements of mechanical support, compartmentalization, storage and sequestration of molecules. This also will have correct porosity allowing for diffusion of soluble molecules and access to cells, exposing ligands for adhesion and proliferation and being degradable by enzymatic mechanisms to allow body directed remodelling.

Web site:

http://www.3gscaff.uu.se

Participants:Coordinator Sweden Germany Sweden Switzerland United Kingdom Prof. Jns Hilborn, Uppsala University, Polymer Chemistry, Uppsala tel: +46 18 471 3839 fax: +46 18 471 3477 Jons.hilborn@mkem.uu.se Thomas Gries, Aachen University of Technology, Institut fr Textiltechnik (ITA), Aachen Mikael Sellman, Karocell Tissue Engineering AB, Stockholm IND Florian Wurm, Swiss Federal Institute of Technology, Lab. Cellular Biotechnology, Lausanne Peter Frey, Lausanne Research Hospital, Dept. of Pediatric Urology, Laboratory for Experimental Pediatric Urology, Lausanne Robert Brown, University College London, Inst. Orthopeadics Musculo-Skeletal Science, London John Michael Garland, Tissue Works Ltd / University of Manchester IND

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

PRODUCTION UNIT FOR THE DECENTRALISED ENGINEERING OF AUTOLOGOUS CELL-BASED OSTEOINDUCTIVE BONE SUBSTITUTESProposal acronym Contract n Duration (starting date) AUTOBONE NMP3-CT-2003-505711 4 years (01.01.04) EC contribution () Instrument Participants 2.296.892 STREP 12

Abstract:Bone is among the most frequently transplanted tissues and autografe account for the majority of bone graft procedures. However, autografts always require a secondary surgery adding high costs to health services, increase patient morbidity and are available in very limited quantities. Therefore, there is widespread interest around the world for programmes to rebuild and restore function of degenerative tissue using artificial implant materials. The enormous need for bone grafts and the recent progresses in biomedical and biomaterial sciences have stimulated the rapid growth and expansion of a new field: bone tissue engineering. However, this approach presents important limits to the transfer from an academic to a routine clinical environment: high cost, difficulties in transferring biological samples between hospitals and centralized "cell factories"; reproducibility due to lack of standards. The aim of this project is to combine the developments in the areas of tissue engineering based on materials and 3D scaffolds development with largely laboratory and few commercial activities in the field of bioreactors and transpose the concepts of tissue engineering and regeneration of the frontiers of new developments: the automated production of autologous bone replacement materials. The goal of this project is to develop a bioreactor that would be set-up within the confnes of a hospital and which would be used to homogenously activate specially designed porous matrices with stem cells from harvested bone marrow aspirates of the patient to produce autologous hybrid bone graft materials. The result would be an innovative technology to produce bone substitute materials having biological properties approaching those of autologous bone, the golden standard of the bone substitute, and would be completely biocompatible. This target will be achieved through the following scientific and technical objectives: 1) design and production of innovative bioreactors, 2) design and production of novel biomaterials and scaffolds architectures tailored for both bioreactor use and bone tissue engineering, 3) validation of the approach in preclinical animal studies.

Web site:

http://istec.cnr.it/autobone

Participants:Coordinator Italy Denmark France Germany Italy Spain Switzerland Dr. Anna Tampieri, Inst. Science & Technology for Ceramics - National Research Council, Faenza tel: +39 05 46 699 740 fax: +39 05 46 463 81 tampieri@istec.cnr.it Naseem Theilgaard, Danish Technological Institute, Taastrup Sren Overgaard, Department of Orthopedics, Odense University Hospita, Odense Marie-Franoise Harmand, Laboratoire d'Evaluation des Matriels Implantables, Martillac Christian Rey, Institut National Polytechnique de Toulouse Achim Stangelmayer, Presens Precision Sensing Gmbh, Regensburg, SME Charles James Kirkpatrick, Johannes Gutenberg University of Mainz Martinetti Roberta, Fin-ceramica faenza, Faenza (Ravenna), SME Rodolfo Quatro, Dipartimento di Oncologia, Biologia e Genetica - Universit di Genova Elena Fuentes Carazo, Fundacion Tekniker, Eibar

Ivan Martin, University of Basel Dr Roberto Tommasini, Millenium Biologix AG, Schlieren-Zrich, SME

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

DEVELOPMENT OF A BIOARTIFICIAL PANCREAS FOR TYPE I DIABETES THERAPY - NANOTECHNOLOGY BIOMATERIAL ENGINEERING TRANSPLANTATIONProposal acronym Contract n Duration (starting date) BARP+ NMP3-CT-2003-505614 3 years (01.01.04) EC contribution () Instrument Participants 2.495.600 STREP 14

Abstract:Four to five million people in Europe and about 80 million worldwide suffer from type 1 diabetes (insulindependent), characterized by a deficiency in insulin secretion resulting in hyperglycaemia responsible for debilitating long-term complications (coronary diseases, acquired blindness, chronic renal failures). Recently developed immunosuppressive protocols improved the success of human allogenic pancreatic islets transplantation. However, such transplantation has severe limitations: the number of available donors and the potential toxicity of the immunosuppressive treatments. To avoid immunosupression, islets could be encapsulated to protect them from the attack of the immune system and thus from rejection. This project intends to develop, improve and validate an efficient reliable bioartificial pancreas for human application. To achieve this ambitious goal, various disciplines are integrated in a true task force of basic and clinical researchers with leading expertise in experimental diabetes and advanced modern material technologies to develop an effective approach for the treatment of type 1 diabetes. The proposed approach takes into account the far-reaching advances in the modern nanosize technology, which are of utmost importance for the success of this challenge. To carry out the project to a successful achievement, the consortium gathers a multidisciplinary group of leading European scientists with complementary competencies, spanding from biomaterials to tissue engineering, and high-tech SMEs. This transnational approach provides convincing solutions to bypass the limitations of traditional treatments of this disease. Such a device will improve the security of adequate insulin administration avoiding both unwanted hypoglycemic and hyperglycemic episodes and thereby improve the quality of life of patients.

Web site:

https://mail.mapr.ucl.ac.be/wws/info/barp

Participants:Coordinator France Belgium France Dr. Alain Belcourt, Centre Europen d'tudes du Diabte, Strasbourg tel: +33 3 90 20 12 13 fax: +33 3 90 20 12 19 ceedab@aol.com Willi-Jean Malaisse, Universit Libre de Bruxelles Patrick Bertrand, Universit Catholique de Louvain Serge Piranda, Statice Sant, Besanon, SME Gilbert Legeay, Association pour les Transferts de Technologies du Mans Marie-Pierre Krafft, CNRS - Institut Charles Sadron, Strasbourg Michel Bonneau, Institut National de la Recherche Agronomique, Jouy en Josas Jorg Kandzia, Cell Concepts, Umkrich, SME Karin Ulrichs, Julius Maximilians University Wrzburg Sigurd Lenzen, Medizinsche Hochschule Hanover Piero Marchetti, Universita Di Pisa Andrea Remuzzi, Instituto Di Ricerche Farmacologiche "Mario Negri", Bergamo Allessandra Gliozzi, Biophysics Laboratory, University of Genova Pedro E. Cruz, Empresa de Consultoria em Biotechnologia, Oeiras, SME

Germany Italy Portugal

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

INTELLIGENT BIOMATERIAL SYSTEMS FOR CARDIOVASCULAR TISSUE REPAIRProposal acronym Contract n Duration (starting date) BIOSYS NMP3-CT-2005-013633 3 years (01.01.05) EC contribution () Instrument Participants 1.999.700 STREP 6

Abstract:Cardiovascular diseases are the most frequent cause of mortality in Europe. Concomitant the main age of the European population will increase significantly in the next decades. To prevent the collapse of the health care system as a result of the unpayable clinic cost, new strategies have to be found. Tissue engineering is such a promising strategy to compensate the disadvantages of conventional cardiovascular prostheses. A tissue replacement, engineered from a patients own cells, which can grow and replace the defective tissue, is here the superlative answer. Therefore the objective of the BioSys project is to develop new intelligent biomaterial systems. Starting from common polymers, a biocompatible fibre with controllable degradation will be developed. The fibre will be tested regarding degradation and biocompatibility. Required surface modifications will be carried out, focusing on the improvement of biocompatibility. Different types of 3D-textile scaffolds will be designed and produced. As example for evaluation and implementation of the new intelligent biomaterial, cardiovascular implants will be evaluated and tissue engineered. The developed biomaterial will be the first material with controllable biodegradability and improved biocompability. A material with these properties is not yet available in Europe or in other countries. European researchers will be the first to develop and use this kind of intelligent biomaterial. BioSys demonstrates the competitiveness of European life science research. The results of the project could be transferred to other medical fields for a long term innovation. The enhancement of knowledge in the field of tissue engineering and the development of new biomaterial will be a huge contribution to increase the living quality of the population of the whole European Community, will reduce the consequential costs in the health care system and guarantee an excellent place in further market of tissue engineered products.

Web site:

http://www.biosys-project.com

Participants:Coordinator Germany Finland Germany Dr. Michael Klppels, 3T TextilTechnologie-Transfer GmbH, Aachen IND tel: +49 241 96 33 750 fax: +49 241 96 33 751 michael.kloeppels@3t-gmbh.de Minna Kellomaki, Pertti Nousiainen & Ville Ella, Tampere University of Technology, Institute of Fibre Materials Science, Tampere Thomas Gries, Marvi Sri Harwoko & Ute Wiesemann, Rheinich-Westflische Technische Hochschule Aachen, Institut fr Textiltechnik, Aachen Stefan Jockenhvel & Jrg Sachweh, University Hospital Aachen, Clinic for thoracic and cardiovascular surgery, Aachen Terry Smith, Abhay Pandit, William Carroll, Yuri Rochev & Valerie Barron, National University of Ireland, National Centre for Biomedical Engineering Science, Galway Simon-Philipp Hoerstrup, University of Zurich, Department of Tissue Engineering and Cell Transplantation (Regenerative Medicine), Zurich

Ireland Switzerland

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

CELL PROGRAMMING BY NANOSCALED DEVICESProposal acronym Contract n Duration (starting date) CellPROM NMP4-CT-2004-500039 4 years (01.03.04) EC contribution () Instrument Participants 17.599.928 IP 27

Abstract:The vision of the IP is - in analogy to analytical High-Throughput Screening systems - to develop an automated device for the imprinting of cells via nanoscaled macromolecular landscapes, the NanoScapes. This will allow, for the first time, to non-invasively produce well-defined populations of individually programmed cells, eventually leading to substantial breakthroughs and numerous applications in the fields of molecular medicine and cellular nano-biotechnology. We will build the NanoLandscaper, a demonstrator for this new generation of nano-biotechnological equipment, the CellPROMs. As the EPROM paved the way to a broad application of microelectronics, CellPROMs will overcome current limits of and revolutionise the existing handling technologies and procedures by automated, compact and parallel yet still individual handling of large numbers of cellular samples. Typical targets will be animal and human adult stem cells. The main task of our IP is to develop procedures and devices for the precise creation of NanoScapes. Although surface imprinting of cells will be realised via artificial nano-biotechnological devices, e.g. nanostructured stamps or beads, these tools are designed according to the natural principles of cellular signalling and differentiation. As nanocomponents are essential to the imprinting process, suitable techniques and principles to form nanoscaled macromolecular patterns on arbitrary surface geometries have to be developed. All components, ranging from the nanoscale of functional interfaces up to the macro level for cell handling, are needed as functional modules, ready for implementation into the demonstrator. The project features multiple nano- and biotechnological challenges. To tackle these, will lead to breakthroughs in nanotechnological device development and, moreover, drastically advance our understanding of biological signals relevant to cellular programming. Once available, CellPROMs will facilitate the transition to a more knowledge-based and less resource-intensive society in Europe.

Web site:

http://www.cellprom.net

Participants:Coordinator Germany Austria Belgium France Germany Prof. Guenter Fuhr, Fraunhofer-Institut fr Biomedizinische Technik (IBMT), St. Ingbert tel: +49 6894 980 0 fax: +49 6894 980 400 guenter.fuhr@ibmt.fhg.de Franz Gabor, Univ. Vienna, Inst. Pharmaceutical Technology and Biopharmaceutics, Vienna Florence Xhonneurx, Eurogentec, Seraing, IND Claude Leclerc, Institut Pasteur, Biologie des Regulations Immunitaires, Paris Uwe Hartmann & Klaus Steingrver, Saarlandes Univ. & Inst. fr Neue Materialien, Saarbrcken Christiane Ziegler, Technische Universitt Kaiserslautern, Kaiserslautern Matin Daffertshofer, Evotec Technologies, Hamburg, IND Jrg Scherer, European Research and Project Office, Saarbrcken Hagen von Briesen, Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt am Main Petra Zalud, tp21, Life Science, Saarbrcken, SME Frank Saurenbach, Surface Imaging Systems (S.I.S.), Herzogenrath, SME Michael Stuke, Max-Planck-Gesellschaft zur Frderung der Wissenschaften,Gttingen Steffen Howitz, Gesellschaft fr Silizium-Mikrosysteme (GeSiM), Grosserkmannsdorf, SME Christian Moormann, AMO, AMICA (Advanced Microelectronic Center Aachen), Aachen, SME Andreas Manz, Institut fr Spektrochemie und Angewandte Spektroskopie, Dortmund Ron Maron, Tel Aviv Univ. Research Institute for Nanoscience and Nanotechnology, Tel-Aviv

Israel Italy Lithuania Portugal Slovenia Spain Sweden Switzerland

Giampaolo Minetti, University of Pavia, Dipartimento di Biochimica Sezione di Scienze, Pavia Aivaras Kareiva, Vilnius Univ., Fac. Chemistry, Depart. General and Inorganic Chemistry, Vilnius Manuel Carrondo, instituto de Biologia Experimental e Tecnologica, Oeiras Sasa Svetina, University of Ljubljana, Faculty of Medicine, Institute of Biophysics, Ljubljana Josep Samitier, Univ. Barcelona, Bioelectronic & Nanobioscience res. center (CBEN), Barcelona Hans Hertz, Kungl Tekniska Hgskolan, KTH Physics, Stockholm Melene Andersson, Silex Microsystems AB, Jarfalla, SME Philippe Renaud, Ecole Polytechnique Fdrale de Lausanne, Lausanne Denis Bubendorf, Sysmelec, Gals, SME Karl Brander, Leister Process Technologies, Microsystems Division, Kgiswil, IND

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G4 Nanosciences andnanotechnologies

THREE-DIMENSIONAL RECONSTRUCTION OF HUMAN CORNEAS BY TISSUE ENGINEERINGProposal acronym Contract n Duration (starting date) CORNEA ENGINEERING NMP2-CT-2003-504017 3 years (01.04.04) EC contribution () Instrument Participants 2.558.797 STREP 15

Abstract:The goal of the proposed research project is to reconstruct a human cornea in vitro, for use both in corneal grafting and as an alternative to animal models for cosmeto-pharmacotoxicity testing. The project responds to the urgent need to develop new forms of corneal replacements as alternatives to the use of donor corneas, in view of of the world-wide shortage of donors, the increasing risk of transmissable diseases, the widespread use of corrective surgery which renders corneas unsuitable for grafting, and the severe limitations of currently available synthetic polymer-based artificial corneas (keratoprostheses). The originality of the proposal lies in the use of recombinant human extracellular matrix proteins to build a nano-engineered scaffold to support growth of the different cell types found in the cornea, cells to be derived from human adult stem cell pools. The development of a reconstructed human cornea will represent a real breakthrough, allowing diseased or damaged corneas to be replaced by tissue-engineered human corneal equivalents that resemble in all respects their natural counterparts. The proposal also responds to impending ED legislation banning the marketing of cosmetic products that have been tested on animals, using procedures such as the Draize rabbit eye irritation test. The development of tissue engineered corneas will provide a non-animal alternative which will therefore alleviate animal suffering. The project will lead to a transformation of industry to meet societal needs using innovative, knowledge-based approaches integrating nanotechnology and biotechnology. The project brings together 14 participants with complementary expertise from 9 different countries, including basic scientists, ophthalmologists and industrialists (3 SMEs). Ethical and standardisation aspects will also be included.

Web site:

http://www.cornea-engineering.org

Participants:Coordinator France Belgium Finland France Dr. David John Stuart Hulmes, CNRS, Institut de Biologie et Chimie des Protines, Lyon tel: +33 4 72 72 26 67 fax: +33 4 72 72 26 04 d.hulmes@ibcp.fr Betty V. Nusgens, University of Lige, Dept. of Preclinical Sciences MI, Faculty of Medicine, Laboratory of Connective Tissue Biology, Lige Eija-Riitta Hamalainen, Fibrogen Europe Oy, Helsinki, SME Jean-Marc Legeais, Assistance Publique - Hpitaux de Paris, Laboratoire Biotechnologie et Oeil, Hopital Hotel-Dieu de Paris Patrick Sabatier, Banque Franaise des Yeux, Paris Pascal Bernard, Laboratoires Ioltech, La Rochelle, SME Eric Perrier, Coletica, R&D Department, Lyon, SME Jurgen Bednarz, Universitatsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fur Augenheilkunde, Hornhautbank Efrat Kessler, Tel Aviv Univ., Goldschleger Eye Research Inst., Sackler Fac. Medicine, Tel Aviv Paolo Rama, Fondazione Centro San Raffaele del Monte Tabor, Ophthalmology Department San Raffaele Hospital, Milan Graziella PELLEGRINI, Fondazione Banca degli Occhi Del Veneto - Epithelial Stem Cell Laboratory - SS. Giovanni e Paolo Hospital, Venice Ake Oldberg, Lunds universitet, Department of Cell and Molecular Biology, Lund Vasif Hasirci, Middle East Technical University Department of Biological Sciences, Biotechnology Research Unit, Ankara Timothy Newson, University of Dundee, Division of Civil Engineering, Dundee

Germany Israel Italy

Sweden Turkey United Kingdom

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G4 Nanosciences andNanotechnologies

SME SUPPLY CHAIN INTEGRATION FOR ENHANCED FULLY CUSTOMISABLE MEDICAL IMPLANTS, USING NEW BIOMATERIALS AND RAPID MANUFACTURING TECHNOLOGIES, TO ENHANCE THE QUALITY OF LIFE FOR EU CITIZENSProposal acronym Contract n Duration (starting date) Custom-IMD NMP3-CT-2006-026599-2 4 years (01.01.2007) EC contribution () Instrument Participants 5.400.000 IP 23

Abstract:The 2010 industry paradigm will be that the Implantable Medical Device surgeon will plan and execute surgical operations based solely on the clinical needs of the patient. Custom-IMD will realise this vision through the development of new biomaterials for the manufacture of innovative fully customised medical implants using enhanced rapid manufacturing technologies; achieving implant design, manufacture, sterilisation, regulatory approval and delivery to the surgeon within a 48 hour time frame. The core project objectives are: - The development of innovative biomaterials (ceramics, bio-passive, bio-active and shape-memory polymers) for use in Rapid Manufacturing. - To undertake in-vitro, cell culture and in-vivo animal studies for the new biomaterials; thus generating a strong toxicological and biocompatibility knowledge base. - To achieve innovations within five Rapid Manufacturing techniques enabling the processing of the selected biomaterials achieving targeted material properties and timeframe. - To achieve integration of the medically certified e-supply chain management (confidential patient data, material supply, implant design and manufacture, sterilisation and certification) enabling customised implants to be supplied to the surgeon within 48 hours. - The design, manufacture and testing of three fully customisable implant products (craniofacial bone plate; lumbar spinal disc replacement; and dental restoration) achieving target implant specifications. - To demonstrate the direct economic savings to the European healthcare service for customisable implants and to quantify their wider economic and societal added value. The project objectives demonstrate high relevance to the NMP objectives, including: industrial transformation towards high-tech / knowledge based processes and products; higher added value (economic competitiveness); the generation of new knowledge; and greater European integration (across science, industry and society)

Web site:

not yet

Participants:Coordinator Spain Belgium Germany Poland Netherlands Mr Manuel Leon, Ascamm, Parc Tecnolgic del Valles, Cerdanyola del Valls, Barcelona, SME tel: +34 935 944 700 fax: +34 935 801 102 melon@ascamm.com Michel Janssens, Materialise, Leuven Thomas Wiest, Bremer Goldschlgerei Wilh. Herbst GmbH & Co, Bremen, IND Michael Shellabear, Electro Optical Systems GmbH, Munich, IND Konrad Wissenbach, Fraunhofer-Institut fur Lasertechnik, Aachen Damian Pustelnik, ENTE sp. z o.o., Gliwice, IND Janusz Marian Rosiak, Centre of Excellence "Application of Laser Techniques and Biomaterials in Medicine", Lodz Joost De Bruijn, Progentix, Bilthoven, SME Anton Bosman, Suprapolix, Eindhoven, SME Mark Welters, Innalox, Tegelen, SME Hanneke Boersma, Strategic Medical Consultants, Leiden Nico F. Kamerman, TNO, Industrie en Techniek, Eindhoven Jules M.N. Poukens, Academish Ziekenhuis Maastricht, Maastricht Vicenc Gilete Garcia, NeoSurgery, Cerdanyola del Valles, SME Liliana Chamudis-Varan, Aimplas, Paterna-Valencia, SME Carlos Atienza, IBV, Universidad Politcnica de Valencia, Valencia Alberto Lombarte, PlastiaSite, Barcelona, SME Carles Rubies, UDIAT, Barcelona, SME Pablo Clavel, Sant Pau Hospital, Barcelona Karl Stadler, Icotec, Altstatten, SME Kurt Ruffieux, Degradable Solutions, Schlieren, SME Habib Hussein, Ideas3, Englefield Green, SME Emyr Peregrine, Rapra Technology Ltd, Shrewsbury, Shropshire, SME

Spain

Switzerland United Kingdom

Commission:

Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

NOVEL THERAPEUTIC STRATEGIES FOR TISSUE ENGINEERING OF BONE AND CARTILAGE USING SECOND GENERATION BIOMIMETIC SCAFFOLDSProposal acronym Contract n Duration (starting date) EXPERTISSUES NMP3-CT-2004-500283 5 years (01.10.04) EC contribution () Instrument Participants 7.300.000 NoE 20

Abstract:The main aim of the proposed network of excellence (NoE) is to combat and overcome fragmentation of European Research on the field of Tissue Engineering of Bone and Cartilage. The network will bring together Europe's leading academic centres and several complementary industrial players in a multi-disciplinary consortium to conduct and structure research that is able to compete in the internationally arena, namely with USA and Japan. The constitution of this NoE will lead to a complete restructuring and reshaping of the European research in this field. The size of the network (20 partners from 13 countries, including 9 of the EU member states), and the selection of its original members, was designed in order to join together the critical mass and all the expertises needed to be an unavoidable world reference on the topic of tissue engineering of bone and cartilage. In order to achieve that, the network also incorporates, as part of an International Advisory Board (not funded by EU), academic partners of leading institutions in the USA, Canada and Singapore. This NoE aims to provide new tissue engineering technologies for therapeutic treatments, which will ultimately have a major social impact by contributing to the challenge of providing lifelong health for our society at an affordable cost. The objective of creating a long lasting structuring effect of the European research on tissue engineering will in fact converge with the overall goal of the Network, which is to establish a sustainable Virtual European Centre of Excellence in Tissue Engineering of Bone and Cartilage that overcomes the fragmentation of European research in this field. Network activities will be organized through a Joint Programme of Activities (JPA) structured in three levels: Joint Programme of Integration (JPI), Joint Programme of Research (JPR), Joint Programme of Spreading (JPS) and Management. The EXPERTISSUES NoE is now focused around 20 core partners that provide the necessary expertise and resources that realistically can be expected to participate on the joint programme of activities. The NoE will be initially composed by 131 researchers (including also 147 registered doctoral students), corresponding to an average annual budget of around 1.83 million .

Web site:

http://www.expertissues.org

Participants:Coordinator Portugal Austria Belgium Czech Republic Finland Germany Israel Italy Spain Sweden Switzerland Turkey United Kingdom Prof. Rui Luis Reis, 3Bs Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. Polymer Eng., University of Minho, Braga tel: +351 253 604 781 / 2 fax: +351 253 604 492 rgreis@dep.uminho.pt Heinz Redl, Ludwig Boltzmann Institute, LBI Trauma Care, Vienna Wilfried Vancraen, Materialise N.V., Leuven, SME Frantisek Rypacek, Acad. Sciences Prague, Dept. Bioanalogous & Biodegradable Polymers Pertti Olavi Tormala, Institute of Biomaterials, Tampere University of Technology Charles James Kirkpatrick, Johannes Gutenberg-University, Institute of Pathology, Mainz Nicole Rotter, Dept. Otorhinolaryngology, University Hospital of Schleswig-Holstein, Lbeck Herma Glockner, CellMed AG, Alzenau, SME Daniel Cohn, Casali Institute of Applied Chemistry, The Hebrew University of Jerusalem Emo Chiellini, Dept. Chemistry and Industrial Chemistry, University of Pisa Claudio Migliaresi, Dipt. Ingegneria Materiali e Tecnologie Industriali, Universit di Trento Bruno Fiorentino, Kedrion S.p.A., Barga, SME Julio San, Roman, Consejo Superior de Investigaciones Cientficas, Madrid

Paul Gatenholm, Dept. Materials & Surface Chemistry, Chalmers Univ. Technol., Gothenburg Ralph Mller, Inst. Biomedical Engineering, Swiss Federal Inst. Technology (ETH), Zurich Jeff Hubbell, Inst. Sci. et ingnierie chimiques, Ecole Polytechn. Fd. de Lausanne (EPFL) Vasif Hasirci, Dept. Biological Sciences, Ankara, Middle East Technical University, Ankara Erhan Piskin, Dept. Chemical Eng., Bioengineering Division, Hacettepe University, Ankara Paul Vincent Hatton, Centre Biomaterials and Tissue Engineering, School Clin. Dentistry, University of Sheffield Alicia Jennifer El Haj, Centre Science and Technol. in Medicine, Keele Univ., Stoke-on-Trent

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

ADULT MESENCHYMAL STEM CELLS ENGINEERING FOR CONNECTIVE TISSUE DISORDERS. FROM THE BENCH TO THE BED SIDEProposal acronym Contract n Duration (starting date) GENOSTEM LSHB-CT-2003-503161 4 years (01.01.04) EC contribution () Instrument Participants 8.752.000 IP 23

Abstract:The objective of this Integrated Project Genostem is to establish an European international scientific leadership foe stem cell regenerative medicine in the field of connective tissue disorders. Autologous adult Mesenchymal Stem Cells (MSCs) are optimal candidates to serve as the building blocks for the engineering of connective tissues since they are the multipotential stem cells that give rise to skeletal cells (osteoblasts, chondrocytes and tenocytes), vascular cells (endothetial cells, pericytes and vascular smooth muscle cells), sarcomeric muscle (skeletal and cardiac), and adipocytes. To our knowledge, there is no systematic study on the different facets of MSC biology and engineering, which is the precise purpose of this project. Genostem will compare different tissue sources of MSCs and isolate MSCs subsets in order to obtain undifferentiated MSCs, committed MSCs at early stage of differentiation, progeny blocked at specific differentiation stage and fully differntiated progeny. Genostem will study the complete MSC gene product repertoire using genomic and proteomic analysis that should provide with the molecules and pathways potentially operative for the maintenance and differentiation of stem cells. Genostem will develop new technologies to generate biodegradable matrices, scaffolds and microcarriers that bind pharmacologically active proteins and allow their delivery in a controlled way; these biomaterials will allow to engineer MSCs such as to obtain optimal repair of the target injured tissue. Genostem will improve methods for gene transfer using original lentivirus or non viral delivery systems (polymersomes and matrix-anchoring, DNA-binding peptides) in order to carry out gain (gene transfer) and loss (siRNA transfer) on function studies. Genostem will develop a number of transplantation models of MSCs mimicking human pathological processes operative in osteoarthritis, rheumatoid arthritis, bone congenital disease, extented bone factures, osteoporosis, tendon injuries, limb and coronary ischemia, cardiopathy, pulmonary arterial hypertensive disease and cancer. The final goal is to develop clinical trials using MSCs, in bone, cartilage and tendon disorders, in partnership with SMEs and regulatory bodies for the scale up of safe procedures, taking advantage of the experience already acquired by one of the partner in clinicals trials using cultured muscle cells. Genostem brings together a combination of expertises in Molecular Biology, Cellular Biology, Biomechanics, Genomics, Proteomics, Bioinformatics and Molecular Medicine. The critical mass achieved by this Consortium that comprises a few hundred researchers from public agencies, universities and SMEs, should enable breakthroughs in MSC engineering directly amenable for clinical applications.

Web site:

http://www.genostem.org

Participants:Coordinator France France Prof. Christian Jorgensen, Institut national de la sant et de la recherche mdicale, Montpellier tel: +33 4 67 33 89 63 fax: +33 4 67 33 77 98 jorgens@montp.inserm.fr Pierre Charbord, Universit Franois Rabelais, Tours Jacques Hatzfeld, Centre National de la Recherche Scientifique, Villejuif Jean-Pierre Pujol, Universit de Caen Jean-Pierre Mouscadet, AbCys SA, Paris, SME Nathalie Rougier, Biopredic International, Rennes, SME Marielle Maurice, Genopoietic S.A.S., Miribel, SME Jonathan Dando, INSERM Transfert SA, Paris Gerhard Gross, German Research Centre For Biotechnology, Braunschweig Christian Peschel, Technische Universitt Munchen Ulrike Nuber, Max Planck Society, Berlin Thomas Hapl, Charit universittmedizin Berlin Helen Papadaki, University of Crete, Fac. Medicine, Haematology Research Lab., Heraklion Maria Kalmanti, University of Crete, Fac. Medicine, Pediatric Hematology - Oncology, Heraklion Dan Gazit, The Hebrew University of Jerusalem Erella Livne, Technion - Israel Institute of Technology, Haifa Paolo Bianco, Universit La Sapienza Roma

Germany

Greece Israel Italy Portugal Romania Spain Swizerland United Kingdom

Nuno M. Neves, University of Minho, Braga Virgil Paunescu, University of Medicine and Pharmacy Victor Babes, Timisoara Jeronimo Blanco Fernandez, Instituto de Ciencias Cardiovasculares de Barcelona Ralph Mueller, Swiss Federal Institute of Technology, Zurich Jason Schense, Kuros Biosurgery, Zurich, SME Jeffrey A. Hubbell, Swiss Federal Institute of Technology, Ecublens Yuti Chernajovsky, Queen Mary & Westfield College, University of London

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

A HYBRID APPROACH FOR BONE AND CARTILAGE TISSUE ENGINEERING USING NATURAL ORIGIN SCAFFOLDS, PROGENITOR CELL AND GROWTH FACTORSProposal acronym Contract n Duration (starting date) HIPPOCRATES NMP3-CT-2003-505758 4 years (01.02.04) EC contribution () Instrument Participants 2.896.000 STREP 7

Abstract:This project aims to provide new tissue engineering technologies for therapeutic treatments, which will ultimately have a major social impact by contributing to the challenge of providing lifelong health for our society at an affordable cost. The main aim is the development of advanced functional materials that are needed for improved quality of life of thousands of patients suffering from cartilage or bone tissue loss or malfunctioning. The improved therapy suggested herein will result in a decreased morbidity and mortality of patients with reduction of the overall costs in EU healthcare. A major objective is the development of tissue engineering (TE) products that can be used for bone TE, cartilage TE or for an osteochondral TE strategy. Natural origin scaffolds mainly based on algae & chitosan will be used for bone and cartilage. Ceramic (bi-phasic calcium-phosphate) scaffolds will be obtained from mineralised red algae. For the osteochondral approach, specific technologies will be developed to produce complex bi-material (polymer/ceramic) constructs. An all range of adequate processing techniques to obtain suitable scaffolds will be developed. One of the main innovations will be the development and use of specific software packages for designing patient specific scaffolds that will be combined with the production of the scaffolds by means of 3D plotting methodologies. Other techniques will include melt based processing and solvent based techniques. The scaffolds will also be loaded with a range of growth factors (GF), including several bone-morphogenetic proteins (BMPs) other GF in the TGF- family. Primary cells and progenitor cells obtained from animals and later on from human patients will be used to develop the tissue engineered products. Cell culturing methodologies will be optimised and specific ways of controlling the cultures evolution into the desired phenotypes will be developed. In-vivo functionality assessment experiments will also be carried out.

Web site:

http://www.hippocratesproject.org

Participants:Coordinator Portugal Austria Belgium Germany United Kingdom Prof. Rui Lus G. Reis, Universidade do Minho, Braga tel: +351 253 604 781 fax: +351 253 604 492 rgreis@dep.uminho.pt Heinz Redl, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna Christian Gabriel, Red Cross Transfusion Service of Upper Austria, SME Michel Janssens, Materialise N.V., Leuve, SME Mr Hendrik John, Envisiontec GmbH, Marl, SME C.J. Kirkpatrick, Johannes Gutenberg University of Mainz Matthew Dring, Queen's University Belfast

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

DEVELOPMENT OF NEW POLYMERIC BIOMATERIALS FOR IN VITRO AND IN VIVO LIVER RECONSTRUCTIONProposal acronym Contract n Duration (starting date) LIVEBIOMAT NMP3-CT-2005-013653 3 years (01.04.05) EC contribution () Instrument Participants 2.299.906 STREP 5

Abstract:The development of new polymeric biomaterials designed to stimulate specific cellular responses at the molecular level such as activation of signalling pathways that control gene activity involved in maintenance, growth, and functional regeneration of liver tissue in vitro could be an important step in tissue engineering. The project is aimed to the development of polymeric synthetic and biodegradable biomaterials to control liver cell responses in vitro and in vivo systems. Isolated hepatocytes are able to continue the full range of known in vivo liver specific functions for only a short time. The in vitro maintenance of competent hepatocytes is decidable so that the liver functions can be studied in a controlled environment. Engineered liver tissue constructs may provide an inexpensive and reliable in vitro physiological model with great control of variables for studying disease, drug, infection and molecular therapeutics. New modified polyetheretherketone PEEK-WC membranes will be prepared in hollow fibre configurations. Membranes will be prepared by phase inversion technique, which permits to obtain membranes with various structural properties by means of kinetic and thermodynamic parameter control. In addition, the development of synthetic polymeric materials consisting of nanofiber network scaffolds represents an entirely new approach to tissue engineering that has relied in the past on materials that where either of unknown composition (i.e. Matrigel) or not possible to design (i.e. Collagens). Thus, the design and preparation of synthetic three-dimensional nanofiber network scaffolds that highly mimic the extra cellular matrix will be a valuable tool in the field. The surface of membranes/scaffolds to be utilized in the project will be modified by non equilibrium plasma-chemical processes such as Plasma Deposition of thin films (PE-CVD) and Plasma Treatments to adapt their properties to the best compatibility with cells. With the same objective, plasma-modified surfaces will be further modified by means of immobilisation reactions of biomolecules able to stimulate specific cellular responses at the molecular and cellular level.

Web site:

http://www.uni-leipzig.de/livebiomat

Participants:Coordinator Germany Germany Italy Spain Prof. Agustinus Bader, University Leipzig, Center for Biotechnology and Biomedicine Cell Techniques and Applied Stem Cell Biology, Leipzig tel: +49 (0)341 97-31351 fax: +49 (0)341 97-31359 augustinus.bader@bbz.uni-leipzig.de Ulrich Grokinsky, LSMW GmbH, Berlin IND Loredana de Bartolo, Inst. Membrane Technology, National Research Council of Italy, Rende Pietro Favia, University of Bari, Department of Chemistry, Bari Carlos E. Semino, Salvador Borrs & Mercedes Balcells, University Ramon Lull, Barcelona Bioengineering Center, Barcelona

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

INTELLIGENT NANOCOMPOSITE FOR BONE TISSUE REPAIR AND REGENERATIONProposal acronym Contract n Duration (starting date) NANOBIOCOM NMP3-CT-2005-516943 3 years (01.05.05) EC contribution () Instrument Participants 2.017.616 STREP 8

Abstract:There are roughly 1 million cases in the USA and 0.5 million in EU of high skeletal defects a year. All of these cases require bone-graft procedures to achieve union, each of which requires the surgeon to determine the type of graft material to be use. The toughest challenge appears when the size of the defect is too big and the reconstruction of this defect requires a bone graft capable of supplying similar physical properties and behavior to the bone being substituted. Unfortunately at this moment commercial scaffolds can not satisfy the following issues: 1) To promote new bone formation in order to reduce the time of bone healing and decrease the vascular insult of the implant to the bone and cause less-stress shielding. 2) Mechanical properties that match those of human tissue to be regenerated during its new formation. 3) Large segment of implants. For patients who have lost large segments of bone due to a congenital defect, degenerative diseases, cancer or accident. Based on these basic needs to provide an ideal scaffold, the NANOBIOCOM project aims at establishing the scientific and technological basis for the development new intelligent composite scaffold for bone tissue repair and regeneration with the following issues: 1) Bioactive behavior capable of activating osteoprogenitor cells and genes and within an in vivo environment provide the interface to respond to physiological and biological changes, 2) Mechanical and structural properties similar to a healthy bone. 3) Size and shape required for reconstructing big skeletal defects NANOBIOCOM focuses on the development of an intelligent material with the following challenges: 1) The bioactivity of the composite, which is rendered by the bioactive components (nanoparticles, carbon nanotubes, polymers) in the composite and/or by external stimulation (BMPs, Electrical Fields, biofunctionalitation) will active osteoprogenitor cells and gens, and consequently promote the tissue growth adjacent to the implant. 2) Mechanical and structural properties of the scaffold equal to a healthy bone synchronous with new bone formation. By the incorporation of nanoparticles as carbon nanotubes and nanohidroxiapatite into the composite are expected to be highly suitable reinforcement for the implants of the load bearing structures of our body such as bone and cartilage. 3) The size and shape of biodegradable implants. We are going made large segments of implants required for reconstructing big defects capable of supplying similar physical properties and behavior of healthy bone to be replaced, in contrast with the small implants that are made at present. 4) Understanding the genetic programming of bone regeneration. To realize the potential for novel intelligent composite materials to serve as scaffolds for bone regeneration requires that the innate programming mechanisms involved in bone development and repair are effectively harnessed. The main output of NANOBIOCOM project will be: 1) An appropriate cell bioactive system to initiate repair and regeneration of bone. 2) Intelligent composite for 3D scaffold, which will be able to support physiological loading until sufficient tissue regeneration occurs and will be possible manufacture large segments. 3) A comprehensive gene expression profiles of the temporal regulation of gene expression during bone development.

Web site:

http://www.nanobiocom.org

Participants:Coordinator Spain Italy Dr. Iaki lava & Maria Jess Jurado, Fundacin Inasmet, , Department of Materials and processes, Donostia-San Sebastian tel: +34943003700 fax: +34943003800 ialava@inasmet.es Jose M. Kenny, Consorzio Interuniversitario Nazionale pa la Scienza dei Materiali, Department of Materials Science and Technology, Terni Gabriela Ciapetti, Nicola Baldini, Donatella Granchi & Elisabetta Cenni, Istituti Ortopedici Rizzoli, Laboratorio di Fisiopatologia degli Impianti Ortopedici, Bologna J.A. Jansen, XF Walboomers, JGC Wolke & J van den Dolder, Stichting Katholiek Universiteit, Department of Periodontology and Biomaterials, Nijmegen Jos L. Peris & Amelia Gmez, Instituto de Biomecnica de Valencia, Implant section, Barcelona Laureano Simon, Lourdes Osaba & Pilar Saenz, Progenika Biopharma S.A., Derio-Vizcaya IND Jaques Lematre, Ecole Polytechnique Federale de Lausanne, Laboratory for Powder Technology, Lausanne Colin McCaig & Ian Gibson, University of Aberdeen, School of medical Sciences, Institute of medical Sciences, Aberdeen

Netherlands Spain Switzerland United Kingdom

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

3G-NANOTECHNOLOGY BASED TARGETED DRUG DELIVERY USING THE INNER EAR AS A MODEL TARGET ORGANProposal acronym Contract n Duration (starting date) NanoEar NMP4-CT-2006-026556 4 years (01.11.2006) EC contribution () Instrument Participants 10.499.957 IP 23

Abstract:The goal of the NANOEAR consortium is to develop novel multifunctional nanoparticles (MFNPs), which are targetable, biodegradable, traceable in-vivo and equipped with controlled drug release. With over 44 million EU citizens with treatable hearing loss, and 40 000 profoundly deaf who can be benefit with MFNP-based novel cochlear implant, the inner ear is a unique target. Both a model for nervous system disorders and difficult-to-access body sites; it is isolated, with neural and vascular targets, and is immuno-privileged. Measures of function and structure are quantitative and precise. Highly penetrating delivery vehicles will be created to carry and release drugs precisely to targeted tissue sites and selected cells. Nanoparticles, dendrimers, micelles and polymer-protein complexes will be designed for delivery of drugs/genes to selected targets of the inner ear. Four EU/FDA approved degradable biomaterials will be tested for targeting, coating, toxicity and payload carrier capacity. Commercially available liposomes, encapsulated by polyethylene glycol (PEG), impregnated with drugs, and modified with targeting ligands and signalling molecules (gadolinium) will be assessed for benchmarking purposes. The fabricated MFNPs will be applicable to wide variety of drugs (e.g. conventional therapeutics, growth factors, proteins, nucleic acids, steroids). We will demonstrate greater selectivity, reduced side effects and greater efficacy than possible with current drug delivery, and provide treatments not currently possible. As a demonstration milestone this IP will produce a novel human cochlear implant promoting improved cochlear nerve-implant integration. In this demonstration the implant will include a MFNP drug reservoir providing continuous drug delivery and MFNP electrode coatings providing targets for nerve growth.

Web site:

not yet

Participants:Coordinator Finland Austria Czech Republic Denmark Finland France Germany Prof. Ilmari Pyykk, Depart. Otolaryngology, Medical Faculty, University of Tampere, Tampere tel: +358 3 31166387 fax: +358 3 31164366 ilmari.pyykko@pshp.fi Annelies Schrott-Fischer, Medizinische Universitt Innsbruck, Innsbruck Claude Jolly, MED-EL Elektromedizinische Gerte GmbH, Innsbruck, SME Josef Syka, Institut of Experimental Medecine, Academy of Sciences of Czech Republic, Prague Marlene Rugaard Jensen, NsGene A/S, Ballerup, SME Prof. Minna Kellomki, Technical University of Tampere, Tampere Prof. Jarl Bjrn Rosenholm, Abo Akademi University, Depart. Physical Chemistry, Turku / Abo Prof. Paavo Kinnunen, Helsingin Yliopisto, Helsinki Patrick Saulnier, University of Angers, Angers Jean-Luc Puel, Institut National de la Sant et de la Recherche Mdicale, UMR 583, Montpellier Thomas Lenarz, Medizinische Hochschule Hannover, Hannover Klaus-Peter Schmitz, Universitt Rostock, Rostock Martin Mller, Rheinisch-Westflische Technische Hochschule Aachen (RWTH), Aachen Joachim Spatz, Ruprecht-Karls-Universitt Heidelberg, Heidelberg Volker Faust, Hemoteq GmbH, Wrselen, SME Elias Lianos, National and Kapodistrian University of Athens, Athens Alessandro Martini, Consorzio Ferrara Ricerche, Ferrara Paolo Pinton, Aequotech S.R.L, Ferrara, SME Mamoun Mohammed, Kungliga Tekniska Hgskolan, Stockholm Helge Rask-Andersen, Uppsala Universitet, Uppsala Harm-Anton Klok, Ecole Polytechnique Fdrale de Lausanne, Lausanne

Greece Italy Sweden Switzerland United Kingdom

Victor Hugh Perry, University of Southampton, Southampton Slava Pavlovets, Yorkshire Bioscience Limited, York, SME

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G4 NS&NT

DEVELOPMENT OF LOAD-BEARING FIBRE REINFORCED COMPOSITE BASED NON-METALLIC BIOMIMETIC BONE IMPLANTSProposal acronym Contract n Duration (starting date) NEWBONE NMP3-CT-2006-026279-2 4 years (01.11.2006) EC contribution () Instrument Participants 4.400.000 IP 16

Abstract:The aim of NEWBONE is to develop fibre reinforced composite (FRC) material load-bearing implant: to produce at prototype level two resorbable fixation devices in knee/shoulder ligament repair and twp non-resorbable bone fixation devices for reconstruction of large bone defects and study the use of developed technologies in complete implants (hip stem, knee) and spine applications. The proposal is high tech SME driven: they represent all the different competence areas needed to develop FRC bone implant. Research institution partners are adding to the competence portfolio and the latest knowledge developed by them is transferred to the use of SMEs. Three major breakthrough innovations are present in the proposal: FRC material is used for load bearing bone implants; bioactive glass and hydroxyapatite is used on the implant-bone interface; a new processing method is applied to allow in-situ modifications of the implant during surgery. The results will cover the gaps that exist in Europe in terms of increased healthcare costs and decreased quality of life of patients as well as of Europe dragging behind US in commercialisation of biomaterials and implant technologies. FRC material will reduce problems caused by stresshielding of currently used metal implants. Use of bioactive glass and hydroxyapatite will foster bone growth and implant attachment. The surface structure will allow for inclusion of drug release functions to prevent infections. Partners include Swiss SME Medacta International SA, producer of hip and knee prosthesis and Finnish company ConMed Linvatec Biomaterials Ltd, producer of sport injury repair systems, both committed to the development of FRC implants to be included to their future product portfolios. Together with all industrial partners involved, the consortium will have the abilities to increase the turnover of European implant industry and take the role of a global leader in the niche sector of FRC load-bearing bone implants.

Web site:

not yet

Participants:Coordinator Finland Belgium Finland France Greece Italy Prof. Pekka Vallittu, Institute of dentistry, University of Turku Dr Saara Lampelo, Business & Life Sci. Turku Polytechnic & AcasiaTrade Ltd Oy, Helsinki, SME tel: +358-400666366 fax: +358-09711711 saara.lampelo@acasiatrade.com Dirk Drees, FALEX Tribology NV, Rotselaar Kaj Koskinen, ConMed Linvatec Biomaterials Ltd, Tampere, SME Matti K. Viljanen, University of Turku, Department of Prosthetic Dentistry and Biomaterials Science - Orthopaedic Research Unit, Turku Biomaterials Centre, Turku Jos Alcorta, Rescoll Technological Centre, Pessac Michalis Vardavoulias, PyroGenesis SA, Lavrion, SME Luigi Paracchini, Ingeo SNC, Varallo Pombia, SME Sergio Paoletti, University of Trieste Gianluigi Carlini, Integra S.r.L., Trieste, SME Diego Basset Materialia S.r.L, San Vendemiano, SME Javier Menendez Medina, NanoBioMatters S.L., Paterna, Valencia, SME Miguel Angel Munarriz Casajus, AIN Centre of Advanced Surface Engineering, CordovillaPamplona Lena Nordholm, University College of Bors, School of Engineering, Polymer technology, Boras Alberto Siccardi, Medacta International SA, Castel San Pietro, SME Thomas Hinderling, Swiss Centre for Electronics and Microtechnology, Neuchatel Edna Murphy, University of Cambridge

Spain Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

DEVELOPMENT AND EVALUATION OF MINERALIZED SILK BASED COMPOSITES FOR ORTHOPAEDIC APPLICATIONSProposal acronym Contract n Duration (starting date) SILKBONE COOP-CT-2005-18060 2 years (01.10.05) EC contribution () Instrument Participants 1.599.304 SME-Coop. Research 8

Abstract:The consortium seeks to develop a highly novel bone substitute material (BSM) from mineralised silk composites for use in medical procedures requiring bone tissue replacement. Spinox have developed Spidrex, a novel silk-silk composite based on a fibre and matrix generated from spider silk analogues. Spidrex is biocompatible, bio-absorbable and has excellent mechanical properties and cell adhesiveness. Pilot studies at Bristol have shown it is rapidly and heavily mineralised by the component of natural bone, hydroxyapatite. Mineralised Spidrex will be developed into a BSM by incorporating osteoinductive factors in the silk matrix and biochemical tailoring both fibre and matrix. Progentix will develop non-foetal stem cell technology with which to seed the BSM. 3H Biomedical and U Kon InPuT will test human cell reaction to BSM in vitro. This will reduce the need for animal trials and allow material modification early in the design process. Soton will optimise bone formation in the BSM in vitro. A cellularised, load bearing, resorbable BSM is unprecedented and will provide entry to a market estimated at 2.5 billion euros. It will be particularly advantageous for the treatment of fractures resulting from osteoporosis and bone lesions in cancer patients. The consortium comprises 3 highly innovative, research based SMEs from 3 member states whose competitiveness will be enhanced by access to this market and by collaboration with the consortium's 5 leading RTDs. Individually, each SME does not have the capability to pursue a project of the above magnitude. Tissue engineering, adult stem cell research and implantable biomaterials have been flagged as future growth markets, keenly pursued in the U.S. and Asia. Developing know-how in these areas, and subsequent dissemination of results in Europe will increase E.U. competitiveness in these burgeoning sectors.

Web site:

http://www.silkbone.org

Participants:Coordinator United Kingdom Germany Netherlands Sweden United Kingdom Dr. Nick Skaer, Oxford Biomaterials Ltd., Newbury, SME tel: +44 (0)1635 237226 fax: +44 (0)1635 237226 n.skaer@oxfordbiomaterials.com Sonja Von Aulock, Center for Health and Consumer Protection, Technology Transfer Center for in vitro Pharmacology and Toxicology, Universitat Konstanz Joost Dick De Bruijn, Progentix BV i.o., Bilthoven, SME Wilhelm Engstrom, Department of Biosciences and Veterinary Public Health, Sveriges Lantbruksuniversitet, Uppsala Bror Morein, 3H Biomedical AB, Uppsala, SME Stephen Mann, school of Chemistry, University of Bristol Fritz Vollrath, department of Zoology, University of Oxford Helmtrud Isolde Roach, Bone and Joint Research Group, Southampton General Hospital, University of Southampton

Commission: Directorate General for Research - Implementation of activities to outsource Directorate - Unit T4 SMEs

INJECTABLE MACROPOROUS BIOMATERIAL BASED ON CALCIUM PHOSPHATE CEMENT FOR BONE REGENERATIONProposal acronym Contract n Duration (starting date) SmartCaP NMP3-CT-2005-013912 3 years (01.05.05) EC contribution () Instrument Participants 1.796.814 STREP 7

Abstract:Osteoporosis and bone degeneration in aging populations as well as bone defects caused by trauma and pathology grounds a societal need for therapeutic products. The main goal and the breakthrough of this project are to implement a novel concept of biomaterials for bone regeneration, with a range of properties that elicit specific cell responses. The biomaterials developed in this project will give improvements in health, quality of life, environment and safety. These multifunctional biomaterials will be injectable, porous, intelligent and biodegradable to promote osteogenesis and angiogenesis. Because these biomaterials will be injectable, they will be applied by means of minimally invasive surgery. This means less suffering by the patient, reduction of health care cost, simple surgical technique and improved working conditions. These biomaterials will be an advantageous alternative to autologous bone due to their large availability and that they can be obtained sterilized right off the shelf.

Web site:

http://www.smartcap.eu

Participants:Coordinator Spain Belgium Germany Ireland Italy Prof. Josep A. Planell, Technical Univ. Catalonia, Dpt. Materials Science & Metal. Eng., Barcelona tel: +34 934 011 612 fax: +34 934 016 706 josep.a.planell@upc.es Etienne Schacht, University of Ghent, Department of organic Chemistry/Polymer materials research group, Ghent Lutz Claes, University of Ulm, Institut fuer Unfallchirurgische Forschung und Biomechanik, Ulm Patrick Prendergast, Trinity College Dublin, Centre for Bioengineering, department of mechanical engineering, Dublin Luigi Ambrosio, Consiglio Nazionale delle Richerche, Institute of Composite and Biomedical Materials, Roma Nicola Baldini, Instituti Ortopedici Rizzoli, Laboratorio di Fisiopatologia degli Impianti Ortopedici, Bologna Matteo Santin, University of Brighton, School of Pharmacy and Biomolecular Sciences, Brighton

United Kingdom

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

A SYSTEMS APPROACH TO TISSUE ENGINEERING PROCESSES AND PRODUCTS BIOMATERIAL ENGINEERING BIOMEDICAL ENGINEERING NANOTECHNOLOGYProposal acronym Contract n Duration (starting date) STEPS NMP3-CT-2005-500465 4 years (01.03.05) EC contribution () Instrument Participants 13.063.154 IP 23

Abstract:Tissue engineering (TE) is a rapidly emerging field aimed at the regeneration of tissues and organs for the treatment of disease and injury. TE is based upon scaffold-guided tissue regeneration, and involves the seeding of porous, biodegradable scaffolds with donor cells, the culture of the resulting biohybrid construct in vitro with or without the use of growth factors and finally the implant of the construct into the patient to induce and direct the growth of new healthy tissue. Current clinical applications of tissue-engineered constructs include engineering of skin, cartilage and bone for autologous implantation. Whilst some technological and clinical success has already been achieved, thus demonstrating the potential for TE to make a significant impact on healthcare, there has been a marked lack of connectivity between different components in TE such as the technological development, the industrial up-scaling, the European regulatory panorama, the ethical consideration, the public awareness and the socio-economical validation. Based upon the hypothesis that the only way to successfully implement TE is to systematically link together all aspects of this multidisciplinary process, STEPS is designed to fill those gaps that presently limit the full exploitation of TE. STEPS address this by introducing a systems approach to TE-related issues to reach an integrated network of TE-related knowledge. Such knowledge-based research is designed to address four distinct applications of tissue engineering, each of which is at a different stage of development and therefore lends itself to different pre or post-commercialization analyses. Specifically, the technological components of the Project will include novel biomaterial development, cell sourcing and manipulation, bioreactor design and the integration of TE constructs into the living host. The programme includes the evaluation of the socio-economic issues related to ethics and health economics. This will include an assessment of the public acceptability of these emerging technologies and the ability of private and public health insurances to efficiently balance innovation and cost containment. The Consortium has therefore put together an objective-driven approach, designed to deliver radical innovations in the long term as well as new processes, methodologies and products in the short and medium term. The current potential world market for TE products is estimated at 100 billion but a poorly integrated infrastructure will be incapable of delivering to this market. We believe that this approach will positively transform the European industrial infrastructure related to the development of Tissue Engineered products and processes and lead to significant benefits for the public.The Consortium comprises 23 partners from 13 European countries. It includes 6 industrial organisations, 4 of whom are SMEs and 17 academic centres. In order to tackle the development of such a highly innovative systems approach to TE, the contribution of a truly multidisciplinary Consortium, of a critical mass in man power, and of substantial financial commitment, is required. These multidisciplinary skills are indeed found only within a European cooperation and all the partners are internationally identified centres of excellence in their respective areas of expertise.

Web site:

http://www.stepsproject.com

Participants:Coordinator Italy Austria Belgium France Finland Germany Ireland Italy Latvia Netherlands Poland Spain Ms Alessandra Pavesio, FAB - Fidia Advanced Biopolymers S.r.l., Abano Terme, IND tel: +39 04 982 328 88 fax: +39 04 982 325 57 E-mail : apavesio@fidiapharma.it Stefan Nehrer, University of Vienna Joseph Selling, Katholieke Universiteit Leuven Michel Therin, Sofradim Production, Trevoux, SME Jean Pierre Boutrand, Biomatech, Chasse sur Rhne, SME Pertti Olavi Tormala, Institute of Biomaterials, Tampere University of Technology Lutz Claes, University of Ulm Michael Sittinger, Medical Faculty Charit Humboldt-University of Berlin Peter McHugh, National University of Ireland, Galway Luigi Ambrosio, Consiglio Nazionale delle Ricerche, Roma Giuseppe Remuzzi, Istituto di Ricerche Farmacologiche Mario Negri, Milano Maurilio Marcacci, Istituti Ortopedici Rizzoli, Bologna Garry Kerch, Riga Stradins Unversity

Jan Feijen, University of Twente, Enschede Jaap Oostra, Applikon Dependable Instruments B.V., Schiedam, SME Malgorzata Lewandowska, Warsaw University of Technology Josep Anton, Planell, Universitat Politcnica de Catalunya, Barcelona

Sweden Switzerland United Kingdom

Lars Hedman, Cell Matrix AB, Gothenburg, SME Anders Lindahl, Goeteborg University Ivan Martin, University of Basel Julian Braybrook, LGC Limited, Teddington, IND David Williams, University of Liverpool Richard Lilford, University of Birmingham Anthony Peter Hollander, The University of Bristol

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

BIOREACTIVE COMPOSITE SCAFFOLD DESIGN FOR IMPROVED VASCULAR CONNEXION OF TISSUE-ENGINEERED PRODUCTSProposal acronym Contract n Duration (starting date) VASCUPLUG NMP3-CT-2005-013811 3 years (01.04.05) EC contribution () Instrument Participants 2.300.000 STREP 8

Abstract:Engineered tissues today in most cases lack of appropriate connexion to the vascular system of the surrounding tissue in the body at the implantation site. Hence the tissues suffer from malnutrition and low gas exchange leading to necrosis. To overcome this bottleneck the strategic objective of this project is to develop a novel threedimensional scaffold structure for improved vascularisation of tissue-engineered products. Application of intelligent biomaterials (bioresorbable stimuli-sensitive polymers) and incorporation of bioactive substances (e.g. growth factors) will enhance a structured vascularisation of tissue-engineered constructs by gradually opening inserted microchannels for vessel ingrowth into cellseeded polymeric scaffolds. Furthermore, the mechanism of induction of secondary angiogenesis by monocytes can be used to promote vascularisation. The signal for the stimulus-sensitive polymer to act (meaning: induction of angiogenesis) is intended to be a pH drop associated with malnutrition of cells. The use of angiogenic factors in promoting vascularisation of tissue-engineered constructs so far was performed by a rather isotropic distribution of factors in the scaffolds preventing the buildup of a gradient of bioactive substances for directed cell growth (angiogenesis). In our approach stimuli-sensitive materials which are available will be tested for their application as switching filaments to open microchannels and guide cells involved in vascularisation and/or provide a gradient for directed cell migration and growth. The composite scaffold giving rise to evolving vessels is intended to allow the vascular connexion to the surrounding tissue in the course of wound healing. The complex bunch of requirements for a functional vascularisation of tissue-engineered products calls for a strong interand transdisciplinary co-operation of chemists, biologists, engineers, physicists and physicians depending on a pronounced cross-frontier collaboration.

Web site:

http://www.gkss.de/euprojekte/PSP6_FP6/VASCUPLUG.html

Participants:Coordinator Germany Germany Greece Hungary Spain Sweden United Kingdom Dr. Barbara Seifert, GKSS Forschungszentrum, Geesthacht GmbH, Institut fr Chemie, Teltow tel: +49 3328 352 482 fax: +49 3328 352 452 Barbara.Seifert@gkss.de Gudrun Knedlitschek, Karl-FriedrichWeibezahn & Alexander Welle, Forschungszentrum Karlsruhe GmbH, Institut fr Biologische Grenzflchen, Karlsruhe Peter Schenck, Dr. Suwelack Skin & Health Care AG, Billerbeck Yannis F. Missirlis, University of Patras, Bioengineering Lab, Patras Gyrgy Kri & Richard Schwab, Semmelweis University Budapest, Cooperative Research Centre, Budapest Mara Jos Alonso, University of Santiago de Compostela, Department de Darmacia e Tecnoloxa Farmaceutica, Faculty of Pharmacy, Santiago de Compostela Yihai Cao, Karolinska Institutet, Microbiology and Tumour Biology Centre, Stockholm David Grant, University of Nottingham, School of MMME, Nottingham

Commission: Directorate General for Research - Industrial Technologies Directorate - Unit G3 Materials

MODELLING Mathematical & biological models, alternatives to animal testing

IN VITRO NEURAL TISSUE SYSTEM FOR REPLACEMENT OF TRANSGENIC ANIMALS WITH MEMORY / LEARNING DEFICIENCIESProposal acronym Contract n Duration (starting date) ARTEMIS LSHB-CT-2006-037862 3 years (01.03.07) EC contribution () Instrument Participants 1.985.420 STREP 8

Abstract:The project concerns the design, development and optimisation of an in vitro system to replace the animal experimentation in pharmacology and toxicology on neural tissues and in particular on memory and learning. The in vitro system will consist of a three-dimensional neural tissue, based on a hydrogel layer bearing neurons generated from mouse embryonic stem cells. The hydrogel layer will be interfaced with multielectrode arrays for electrical stimulation and recording purposes. Our objective is to use in vitro developed neural tissues instead of transgenic animals carrying memory and learning deficiencies and, for this reason, our system will be formed by mutated cell lines. Our approach will replace the use of transgenic animals or (at least) provide preliminary information at the tissue level to orient the design of the transgenic animals towards the optimal ones decreasing this way the number of animals that are currently created (and sacrificed) by trial-and-error methods. In addition the system will be used in neurotoxicity tests to correlate measurements at sub-cellular, cellular and synaptic network levels as an integrated set with in vivo-like effects on in vitro memory/learning, setting the methodological basis for the design of complementary in vitro tests needed to predict human hazards. The partners of the ARTEMIS constitute an effective consortium that includes experimental and computational biomedical and biomaterial specialists along with animal experiments labs and standards professionals in this field. The SMEs participation in the ARTEMIS project is significant due both to the importance of their contribution at scientific and technological level but also to the important benefits they will obtain from the outcomes of the project.

Web site:

not yet

Participants:Coordinator Spain Belgium Czech Republic Estonia Hungary Italy Poland Prof. Panetsos Fivos, Departamento de Matematica Aplicada, Universidad Complutense De Madrid, Madrid tel: +34 913946900 fax: +34 913946885 neuro.projects@opt.ucm.es Kotzias Dimitrios, Institute for Health and Consumer Protection, Joint Research Centre, Ispra (Va), Bruxelles Daniel Horak, Department of Bioanalogous and Special Polymers, Group of Polymer Particles, Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague Eero Vasar, Department of Physiology, University of Tartu, Visgenyx, Tartu, SME Andras Janos Dinnyes, BioTalentum Ltd., Godollo, SME George Szekeres, Laboratory of Histopathology, Histopathology Ltd., Pcs, SME Novellino Antonio, eTT - Electronic Technology Team, Genova, SME Janusz Marian Rosiak, Institute of Applied Radiation Chemistry, Lodz

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

DEVELOPMENT OF A HIGH THROUGHPUT GENOMICS-BASED TEST FOR ASSESSING GENOTOXIC AND CARCINOGENIC PROPERTIES OF CHEMICAL COMPOUNDS IN VITROProposal acronym Contract n Duration (starting date) CARCINOGENOMICS LSHB-CT-2006-037712 5 years (01.11.06) EC contribution () Instrument Participants 10.440.000 IP 20

Abstract:The major aim of CARCINOGENOMICS is to develop in vitro methods for assessing the carcinogenic potential of compounds, as an alternative to current rodent bioassays for genotoxicity and carcinogenicity. The major goal is to develop a battery of mechanism-based in vitro tests accounting for various modes of carcinogenic action. These tests will be designed to cover major target organs for carcinogenic action e.g. the liver, the lung, and the kidney. The novel assays will be based on the application of "omics" technologies (i.e. genome-wide transcriptomics as well as metabonomics) to robust in vitro systems (rat/human), thereby also exploring stem cell technology, to generate "omic" responses from a well-defined set of model compounds causing genotoxicity and carcinogenicity. Phenotypic markers for genotoxic and carcinogenic events will be assessed for the purpose of anchoring gene expression modulations, metabolic profiles and mechanism pathways. Through extensive biostatistics, literature mining, and analysis of molecular-expression datasets, differential genetic pathways will be identified capable of predicting mechanisms of chemical carcinogenesis in vivo. Furthermore, generated transcriptomic and metabonomic data will be integrated into a holistic understanding of systems biology, and applied to build an iterative in silico model of chemical carcinogenesis. Subsequently, predictive gene expression profiles, typically consisting of some 150-250 genes, will be loaded onto high throughput dedicated DNA-chips, thus accelerating the analysis of transcriptomic responses by a factor of 100. It is expected that the outcome of this project will generate a platform enabling the investigation of large numbers of compounds for their genotoxic and carcinogenic potential, as envisaged under the REACH initiative. This will contribute to speeding the identification of potential harmful substances to man, while lowering costs and reducing animal tests.

Web site:

not yet

Participants:Coordinator Netherlands Austria Belgium Prof. Jos Kleinjans, Health Risk Analysis and Toxicology (GRAT), Maastricht University tel: +31-43-3881096 fax: +31-43-3884146 j.kleinjans@hb.unimaas.nl Paul Jennings, Department of Physiology and Medical Physics, Division of Physiology, Renal Physiology, Innsbruck Medical University, Innsbruck Raffaella Corvi, Institute for Health and Consumer Protection / European Centre for Validation of Alternative Methods, European Commission - DG JRC, Ispra (Italy), Brussels Arthur van Iersel, ECOPA-BOARD, European Consensus Platform for Alternatives, Brussels Vera Maria Rogiers, Department of Toxicology Dermato-Cosmetology and Pharmacognosy, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel Erwin Roggen, Department of Pharma-Protein Development, Novozymes AS, Bagsvaerd, IND Christophe Chesne, BIOPREDIC INTERNATIONAL, Rennes, SME Susanna-Assunta Sansone, European Bioinformatics Institute (EBI), Microarray Informatics Team, European Molecular Biology Laboratory, Cambridge (UK), Heidelberg Ralf Herwig, Max Planck Institute for Molecular Genetics, Department of Vertebrate Genomics, Max Planck Society, Berlin Michael P. Ryan, UCD School of Biomolecular and Biomedical Science, Conway Institute, National University of Ireland, Dublin John P. Groten, Business Unit Physiological Sciences, TNO Quality of Life, Netherlands Organisation for Applied Scientific Research, Zeist, Delft Tim Kievits, Research Institute NUTRIM, PamGene International B.V., s-Hertogenbosch, SME Jan Boei, Department of Toxicogenetics, Leiden University Medical Center, Leiden Jos Castell, Research Center, Fundacion Hospital Universitario La Fe, Valencia Myriam Fabre, Advanced in vitroCell technologies, Barcelona, SME Petter Bjrquist, Cellartis AB, Gothenburg, SME Andreas Hohn, Genedata AG, Basel, SME Paul Carmichael, Safety and Environmental Assurance Centre, Unilever, Bedfordshire, IND Edward Lock, School of Biomolecular Sciences, Liverpool John Moores University, Liverpool Hector Keun, Biological Chemistry, Division of Biomedical Sciences, Imperial College London

Denmark France Germany

Ireland Netherlands

Spain Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

DEVELOPING A VIRTUAL AND MOLECULAR CONTROL BOARD FOR DIVERTING CANCER STEM CELL TO NON-MALIGNANCEProposal acronym Contract n Duration (starting date) CONTROL CANCER STEM FP6-2003-NEST-B1-12930 3 years (01.10.05) EC contribution () Instrument Participants 1.499.892 NEST-ADVENTURE 4

Abstract:Over the past few years, evidence has accumulated supporting the hypothesis that cancer robustness may be attributed to a small portion of the tumour mass, the cancer stem cells (CSCs). This leads us to propose a more target-oriented treatment for cancer. Our approach is geared towards the addition of Master Switch factors in the microenvironment of the CSCs that will lead to their differentiation into non-proliferative and non-malignant cells. These master switch factors are normally present in the normal stem cell niche to regulate homeostasis. Our proposal is subdivided in in vitro studies, in silico modelling and in vivo testing (transplantation in animal models) of stem cells representing two types of solid tumours: brain and breast cancers. To achieve our goal, the master switch factors will be identified and delivered locally, in and around the tumour. For that purpose, we will use microbeads loaded with the Master Switch protein(s) to deliver, only locally, a high concentration of the differentiating factor(s), recreating a normal microenvironment. Since it relies on the addition of proteins in the environment of the cancer stem cells, we will use a lab-on-chip system to cultivate and study a small number of CSCs in a controlled microenvironment. Finally, it is known that not all tumours even of a same type respond in the same way or at the same speed to an identical treatment. We therefore propose to develop biomathematical models of the behaviour of the CSCs based on parameters identified first in vitro and later in vivo. This biomodelisation will help generating the control board, a realistic predictive model aiming at the custom-tailoring of the tumour treatment. We will then be able to propose a conceptually novel treatment that will include an approach, the facilitation of CSC differentiation, an evaluation method using biopsies in combination with the lab-on-chip and detailed treatment procedures based on predictions by the control board.

Web site:

http://we.vub.ac.be/~cege/leyns/collaborations.html#ccs

Participants:Coordinator Belgium Germany Israel United Kingdom Prof. Luc Leyns, Vrije Universiteit Brussel, Department of Biology, Lab of Cell Genetics, Brussels tel: +32 2 629 3443 fax: +32 2 629 2759 lleyns@vub.ac.be Claus Duschl, Department of Cellular Biotechnology and Biochips (IMBT), Fraunhofer Institute of Biomedical Engineering, Munchen Zvia Agur, Institute for Medical Biomathematics, Bene Ataroth Robert B. Clarke, Dept. of Medical Oncology Breast Biology Group, University of Manchester

Commission: Directorate General for Research - Idea programme Directorate - Unit S2

REDUCING ANIMAL EXPERIMENTATION IN DRUG TESTING BY HUMAN CARDIOMYOCYTE IN VITRO MODELS DERIVED FROM EMBRYONIC STEM CELLSProposal acronym Contract n Duration (starting date) INVITROHEART LSHB-CT-2007-037636 3 years (01.01.07) EC contribution () Instrument Participants 2.701.611 SME-STREP 9

Abstract:The objective of the proposal is to establish stable cell lines that reliably reflect human cardiomyocyte properties by the development of models derived from human embryonic stem cells. The aim is to deliver reliable in vitro models that could be used by the pharmaceutical industry to replace experimental animals in: (1) investigations on pharmacological toxicity and safety of compounds in the drug discovery and development processes, and (2) the testing of toxic effects of chemicals according to the new system of the Community on the Registration, Evaluation and Authorisation of Chemicals (REACH). In the pharmaceutical industry reliable in vitro cell models would contribute to replace current techniques with animal experimentation in the selection and optimisation of lead compounds and in documentation of a selected drug candidate before it enters clinical phases. In the toxicity testing of chemical substances replacement of animal testing methods can be attained as well. The means to accomplish the objective are in addition to new stable human embryonic stem (hES) cell derived cardiomyocytes, (1) state of the art methods for electrophysiological cardiac cell monitoring, (2) optical micro-sensor monitoring in micro-cultivation systems for in vitro screening, (3) a multi-micro-bioreactor platform for high-throughput screening of drugs and chemicals. Comparative studies of cardiomyocytes derived from hES cells with established in vitro models will be carried out in order to validate the new models and methods. The outcome of the project is new efficient in vitro pre-validation models which will significantly reduce animal experimentation for cardiotoxicity testing by 60-80%. Furthermore, it will strengthen the possibility for the participating SMEs to market new potential products in the areas of in vitro assay methods and in vitro compound screening. The SMEs part in this proposal is substantial and the share of the requested budget for the SMEs is 59%.

Web site:

http://www.invitroheart.org

Participants:Coordinator Sweden Belgium Denmark Germany Prof. Carl-Fredrik Mandenius, IFM Biotechnology, Linkping University, Linkping tel: +46 13 288967 fax: +46 13 288979 cfm@ifm.liu.se Susanne Bremer, Institute for Health & Consumer Protection, European Centre for the Validation of Alternative Methods, European Commission, DG Joint Research Centre, Ispra, Brussels Morten Laursen, Department 856, Safety Pharmacology, H. Lundbeck A/S, Valby, IND Karl-Heinz Boven, Multi Channel Systems MCS GmbH, Reutlingen, SME Christine Batzl-Hartmann, Pharmacelsus GmbH, Saarbrcken, SME Achim Stangelmayer, PreSens Precision Sensing GmbH, Regensburg, SME Elmar Heinzle, Biochemical Engineering, Universitt des Saarlandes, Saarbrcken Peter Sartipy, Cellartis AB, Gteborg, SME Anders Lindahl, Department of Clinical Chemistry & Transfusion Medicine, Gteborgs Universitet, Gteborg

Sweden

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

MODELING, MATHEMATICAL METHODS AND COMPUTER SIMULATION OF TUMOUR GROWTH AND THERAPYProposal acronym Contract n Duration (starting date) M3CS-TU TH MRTN-CT-2003-044914 4 years (01.06.2004) EC contribution () Instrument Participants 2.942.447 Marie-Curie RTN 12

Abstract:Tumor evolution is a very complex process, involving many different phenomena, which occur at different scales. From the modelling point of view there are three natural scales of interest: the sub-cellular scale, the cellular scale and the macroscopic scale. The main objective of the project is to organise human capital, activities, structures, management in common to develop mathematical models, algorithms, and computer software for the simulation of multiscale modeling in cancer. The successful development of the project requires a synergy of research efforts and knowledge of mathematics, biology, medicine, computer science, chemistry, and physics. In addition, it requires the development of different phases referring to the modelling process: phenomenological observation, mathematical modelling, mathematical methods, simulation, prediction, experiments, model validation and refinement. The development of all this requires an interdisciplinary approach. The objectives are: 1. Developing the whole modeling process from phenomenological observation to simulation and validation, through the design of mathematical models and their qualitative and quantitative study, in order to simulate tumour evolution within the full range of scales: from sub-cellular to macroscopic. 2. Linking all above approaches, in order to gain deeper insight into the dynamics of tumour growth. 3. Developing predictive, quantitative mathematical models which can be used by clinicians in the fight against cancer as a support to experimental research. 4. Modeling the action of specific therapies to combat cancer, e.g. control of angiogenic phenomena, activation of the immune response, application of chemotherapeutical actions. 5. Developing computational schemes and simulation tools for the benefit of users active in immunology, cell biology, and medicine who are not necessarily expert in mathematics or computer sciences. The design of specific simulation tools can be a very useful bridge between applied mathematicians and bioscientists and can help reducing lab experiments and optimising otherwise frustrating therapies.

Web site:

http://calvino.polito.it/~mcrtn

Participants:Coordinator Italy France Germany Dr. Nicola Bellomo, Dipartimento di Matematica, Politecnico di Torino, Torino tel: +39 0115647514 fax: +39 011 5647599 nicola.bellomo@polito.it Claude Verdier, Laboratoire de Spectrometrie Physique, Universite Joseph Fourier, Grenoble Benoit Perthame, Dept. de Mathematiques et Applications, Ecole Normale Superieure, Paris Uwe an der Heiden, Dept. Mathematics and Theory of Complex Systems, University of Witten/Herdecke, Witten Andreas Deutsch, Center for High Performance Computing, Technical University of Dresden, Dresden Daphne Manoussaki, FORTH, Institute of Applied and Computational Mathematics, Foundation for Research and Technology, Crete Zvia Agur, Institute for Medical BioMathematics, Bene Ataroth Miroslaw Lachowicz, Department of Mathematics, Computer Sciences and Mechanics, University of Warsaw, Warsaw Miguel Angel Herrero, Departamento de Matematica Aplicada, Facultad de Matematicas, Universidad Complutense Madrid , Madrid Magnus Willander, Laboratory of Physical Electronics and Photonics, School of Microtechnology, Gothenburg University and Chalmers University of Technology, Gothenburg Helen Byrne, Centre for Mathematical Medicine, School of Mathematical Sciences, University of Nottingham, Nottingham Mark Chaplain, The SIMBIOS Centre, Division of Mathematics, University of Dundee, Dundee

Greece Israel Poland Spain Sweden United Kingdom

Commission: Directorate General for Research - Human ressources and Mobility Directorate - Marie Curie Actions

TOWARDS THE NEURONAL MACHINEProposal acronym Contract n Duration (starting date) NEURO FP6-2003-NEST-B1-12788 3 years (01.05.2005) EC contribution () Instrument Participants 1.945.500 NEST-ADVENTURE 5

Abstract:Artificial intelligence, computer vision and robotics are limited in their development and practical application because they require highly parallel processing, but usually run on the existing computers which are serial machines i.e. with the wrong hardware. In order to develop highly parallel machines many directions are being explored, like cellular silicon structures, quantum computing, optical computing and biocomputing. Advances in the biocompatibility of materials and electronics have allowed neurons to be cultured directly on metal or silicon substrates, so called Multi-Electrode Arrays (MEA), through which it is possible to stimulate and record Neuronal electrical activity. Therefore, it is desirable to explore the possibility of using biological neurons as computing elements in tasks commonly solved by conventional silicon devices. The aim of the Neuro project is to make further advances in the development of a Neurocomputer, which in 5 or 10 years may become a commercially viable new computational device. This new device is based on arrays of living neurons and capable of massive parallel processing with a parallelism level and a computational speed not achievable with the present silicon technology. The project is based on experimental results already obtained on small-scale devices, and will be based on the solution of three major problems which Neurocomputers have to solve in order to become effective new computing devices: - 1 Neuronal (Wetware) Technology: it is necessary to have control of the wetware, i.e. the biological computing elements. Therefore it is necessary to select and standandize the neurons composing the culture. 2 Hardware development: It is also necessary to develop MEA with a larger number of electrodes with appropriate software and hardware capability. - 3 Algorithmic Analysis and software development: it is necessary to understand which computational problems of Artficial Intelligence, Robotics and Computer Science can be solved with Neurocomputers and which Wetware is the most appropriate for specific problems. Therefore the present consortium brings together one of the best known European specialists in Neuronal stem cells, the leading European manufacturer of MEA and three scientists experienced in the use of MEAs who have a strong background in neuroscience, computer science and computational neuroscience. This combination of partners has all the expertise required to successfully accomplish the project aims.

Web site:

not yet (planned for 2007)

Participants:Coordinator Italy Germany Italy United Kingdom Prof. Vincent Torre, Neurobiology Sector, Scuola Intern. Superiore di Studi Avanzati, Trieste tel: +39 040 3756520 fax: +39 040 2240470 torre@sissa.it Karl-Heinz Boven, Multi Channel Systems MCS GmbH, Reutlingen, SME Ad Aertsen, Dept. of Neurobiology and Biophysics, Albert-Ludwigs-University Freiburg Angelo Vescovi, Dipartimento di Biotecnologie e Bioscienze (BtBs), Universit degli Studi di Milano-Bicocca (UNIMIB), Milan Hugh Robinson, Department of Physiology, University of Cambridge

Commission: Directorate General for Research - Idea programme Directorate - Unit S2

SHORT-TERM IN VITRO ASSAYS FOR LONG-TERM TOXICITYProposal acronym Contract n Duration (starting date) PREDICTOMICS LSHB-CT-2004-504761 3 years (01.09.04) EC contribution () Instrument Participants 2.259.754 STREP 13

Abstract:The development of new pharmaceutical compounds will be more efficient if human relevant toxicology information early in the selection process is available. While acute toxicity can be reasonably detected during the early preclinical stages of drug development, long-term toxicity is more difficult to predict, relying almost exclusively on animal experiments. Animal experimentation of this kind is expensive and time consuming, raises ethical issues and does not necessarily represent a toxicological relevance to man. This project addresses the urgent need to develop in vitro based systems which are capable of predicting long term toxicity in humans. The major objectives of this project are: 1) To develop advanced cell culture systems which as best possible represent the human liver and kidney in vivo. This will be achieved using combined strategies namely: co-cultures of resident cell types, target cell transformation, stem cell technology and new developments in organotypic cell culture (i.e. perfusion cultures and 3D cultures). 2) To identify specific early mechanistic markers of toxin induced cell alterations by using integrated genomic, proteomic and cytomic analysis. 3)To establish and prevalidate a screening platform (cell systems together with analysis tools) which is unambiguously predictive of toxin induced chronic renal and hepatic disease. This proposal is unique in it's mechanistic integration of the three levels of cellular dynamics (genome, proteome and cytome) together with advanced cell cultur technology to detect early events of cellular injury. Only with such an integrated approach will in vitro techniques ever be applicable to predicting chronic toxicity in man. This project, if successful will (1) contribute to the replacement of animal testing in drug development, (2) increase the speed the cost of bringing new pharmaceutical compounds to the patient and (3) increase our understanding of toxin induced chronic renal and hepatic disease.

Web site:

http://www.predictomics.com

Participants:Coordinator Spain Austria Belgium France Germany Ireland Italy Netherlands Spain Switzerland Dr Dr Jos Castell Ripoll, Fundacin Hospital "La Fe", Valencia tel: +34 96 1973 048 fax: +34 96 1973 018 jose.castell@uv.es Walter Pfaller, University of Innsbruck Vera Maria Rogiers, Vrije Universiteit Brussel Philippe Vanparys, Janssen Pharmaceutica N.V., Beerse, IND Bernward Garthoff, European Consensus Platform on 3R-Alternatives, Brussels Patrick Maurel, Institut National de la Sant et de la Recherche Mdicale, Montpellier

Gabriele Scholz, Bayer AG, Wuppertal, IND Michael P. Ryan, National University of Ireland, Dublin Thomas Hartung, Joint Research Centre, Ispra Mohammed Daha, Leiden University Medical Centre Gorka Ochoa, Medplant Genetics S.L., Baracaldo, SME Manzanares Ignacio, PharmaMar S.A. Sociedad Unipersonal, Colmenar Viejo Madrid, SME Armin Wolf, Novartis Pharma AG, Basel, IND

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

DEVELOPMENT OF A NOVEL APPROACH IN HAZARD AND RISK ASSESSMENT OR REPRODUCTIVE TOXICITY BY A COMBINATION AND APPLICATION OF IN VITRO, TISSUE AND SENSOR TECHNOLOGIESProposal acronym Contract n Duration (starting date) ReProTect LSHB-CT-2004-503257 5 Years (01.07.04) EC contribution () Instrument Participants 9.100.000 IP 26

Abstract:Validated alternative test methods are urgently required for safety toxicology of drugs, chemicals and cosmetics. While some animal tests for topical toxicity have been successfully replaced one by one by alternative methods, systemic toxicities require new test strategies in order to achieve an adequate safety level of the consumer. In the project, ECVAM (the European Centre for the Validation of Alternative Methods) will support the management of developing a conceptual framework in the area of reproductive toxicity. The involvement of all stakeholders in the Project Board including the European Consensus Platform on Alternatives (ECOPA), European regulators, OECD, and Industry guarantees an efficient problem solving approach. Reproductive toxicity offers the opportunities that: (i) a substantial number of animals are currently required in in vivo assays; (ii) the reproductive system can be broken down into well-defined sub-elements covering the reproductive cycle; (iii) a number of pioneering alternatives have already been developed; and (iv) the same animal experiments are carried out for drugs, chemicals and cosmetics. The project is composed of four elements, i.e. (a) technological development of in vitro and (b) sensor technologies (c) the strategical development of a conceptual framework (d) the dissemination and implementation activities The project will develop the concepts required to compose testing strategies via the continuous implementation of novel in vitro and in silico alternatives. Problems to be solved include the development of substantial numbers of alternative test methods making use of advanced technologies. This approach requires the dimensions of a transnational Integrated Project, involving some of the most prominent reproductive toxicity research groups in the EU, close monitoring by and input from the regulatory community and professional managerial steering. In return, it offers the realistic opportunity to achieve a substantial reduction of animal experimentation.

Web site:

http://ecvam.jrc.it

Participants:Coordinator Germany Austria Belgium Dr Michael Schwarz, Eberhards Karls Univ. Tbingen, Institute of Pharmacology and Toxicology tel: +49 7071 29 77398 fax: +49 7071 29 77398 reprotect@uni-tubingen.de Alois Jungbauer, Institute of Applied Microbiology, Vienna Johan Smitz, Vrije Universiteit Brussel Jean Mesens, Janssen Pharmaceutica NV, Beerse, IND Rita Goergette Cortvrindt, EggCentris NV, Zellik, SME Hilda Witters, Vlaamse Instelling voor Technologisch Onderzoek, Mol Mekenyan Ovanes, Bourgas University

Bulgaria Denmark France Germany

Elisabeth Ehlert Knudsen, University of Copenhagen Anne Tilloi, Pfizer PGRD, Amboise, IND Horst Spielmann, Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergnzungsmethoden zum Tierversuch (ZEBET), Berlin Alexius Freyberger, Bayer Healthcare AG, Wuppertal, IND Andre Schrattenholz, ProteoSys AG, Mainz, SME Hans Nau, School of Veterinary Medicine, Hannover Corinna Hermann, Steinbeis Technology Transfer Center, Konstanz, SME Giovanna Lazzari, Consorzio per l'Incremento Zootecnico srl, La Serra di San Miniato, SME Alberto Mantovani, Istituto Superiore di Sanit, Rome Andrea Galli, Istituto Sperimentale Italiano Lazzaro Spallanzani, Milano Marcello Span, Ente Per Le Nuove Tecnologie lEnergia e l'Ambiente, Roma Thomas Hartung, EU Joint Research Centre, Ispra Axel Themmen, Erasmus MC, Rotterdam Bart Van Der Burg, BioDetectionSystems BV, Amsterdam, SME Aldert Piersma, National Institute for Public Health and the Environment, Bilthoven Ine Waalkens-Berendsen, Netherlands Organization for Applied Scientific Research, Delft Lennart Dencker, Uppsala universitet Ilpo Tapani Huhtaniemi, Imperial College, London Mark Timothy David Cronin, John Moores University, Liverpool

Italy

Netherlands

Sweden United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

REDUCING ANIMAL EXPERIMENTATION IN PRECLINICAL PREDICTIVE DRUG TESTING BY HUMAN HEPATIC IN VITRO MODELS DERIVED FROM EMBRYONIC STEM CELLSProposal acronym Contract n Duration (starting date) VITROCELLOMICS LSHB-CT-2005-018940 3 years (01.01.06) EC contribution () Instrument Participants 2.942.000 STREP 9

Abstract:The objective of the proposal is to establish stable cell lines that reliably reflect human hepatic properties by the development of models derived from human embryonic stem cells (hESC). The aim is to deliver reliable in vitro models that can be used by the pharmaceutical industry to replace experimental animals in investigations on human drug metabolism, uptake and efflux properties of compounds in the drug discovery and development processes. In the pharmaceutical industry reliable in vitro cell models would replace current techniques and animal experimentation in the selection and optimisation of lead compounds and in documentation of a selected drug candidate before it enters clinical phases. ? The means to accomplish the objective are in addition to hESC derived hepatocytes, (1) 3D-hepatic cell methods, (2) micro-cultivation monitoring for in vitro screening, (3) genomic and metabolomic characterization, and (4) a multi-micro-bioreactors for high-throughput screening of drug candidates. Comparative studies with established in vitro models will be carried out to validate the new models/methods. ? The outcome of the project is new pre-validation models which will reduce the use of animal experimentation for prediction of human drug metabolism and disposition by 60-80%. In addition, the models will also increase safety and quality of compounds chosen as candidates in the different stages of the drug discovery and development process. Furthermore, it will strengthen the possibility for SMEs to market new potential products for assays and in vitro screening. ? The clinical expertise in the project includes two renowned European university hospitals, one SME founded by another European university hospital, and a larger pharmaceutical company. The coordinator and several partners have a background from pharmaceutical industry which is paired with partners very experienced in bioengineering.

Web site:

http://www.vitrocellomics.org

Participants:Coordinator Sweden Belgium Germany Prof. Carl-Fredrik Mandenius, Institute of Technology, Linkping University, Linkping tel: +46 13 288967 fax: +46 13 122587 cfm@ifm.liu.se Sandra Coecke, Institute for Health and Consumer Protection, Joint Research Center, Ispra (VA), Bruxelles Elmar Heinzle, Technische Biochemie, Universitt des Saarlandes, Saarbrcken Jrg Gerlach, Division of Experimental Surgery, Clinic for General, Visceral and Transplantation Surgery, Charit University Medicine Berlin Ruth Maria Maas, Pharmacelsus GmbH, Saarbrcken Manuel Carrondo, Animal Cell Technology Laboratory, Instituto de Biologia Experimental e Technolgica, Oeiras nger Johansson, Division of Molecular Toxicology, IMM, Karolinska Institutet, Karolinska Institutet, Stockholm Petter Bjrquist, Cellartis AB, Gteborg, SME Tommy B. Andersson, AstraZeneca R&D Mlndal, DMPK and Bioanalytical Chemistry, AstraZeneca AB, Mlndal, IND

Portugal Sweden

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

REPAIRING Preclinical and clinical studies for diseases and impairments

BETA CELL PROGRAMMING FOR TREATMENT OF DIABETESProposal acronym Contract n Duration (starting date) BETACELLTHERAPY LSHM-CT-2005-512145 5 Years (01.04.05) EC contribution () Instrument Participants 11.788.000 IP 22

Abstract:Diabetes is a frequent chronic disease that reduces quality of life and increases risks for life-threatening complications. Its onset in younger patients is caused by massive losses in insulin-producing beta cells. Regenerating a functional beta cell mass is thus a major goal in biomedicine and in society. Beta cell grafts prepared from human pancreases can cure the disease but development of this form of beta cell therapy is hindered by shortage in donor organs. Our consortium with leading teams in molecular, developmental and functional biology has worked out an integrated program to generate insulin-producing beta cells in therapeutic quantities and established interactions to translate knowledge to associated bioindustry and multicenter clinical trials, as well as to society. Nature's biologic program to develop and preserve a functional beta cell mass throughout life is taken as platform for directing strategies towards laboratory production of a therapeutic beta cell mass. Beta cells will be derived from embryonic stem cells and from transdifferentiating liver, intestinal and pancreatic exocrine cells. Functional genomics will be used to compare phenotypes of beta cells from new sources with those isolated from the pancreas. This analysis will direct further research and judge on the start of preclinical testing. It will also generate new tools and quality control criteria that will allow standardization of ongoing trials and adjustments in graft biology to increase its long-term survival and function in patients. The consortium considers its plan realistic in its perspective to help develop a cure for diabetes by (re)programming cells for beta cell therapy.

Web site:

http://www.betacelltherapy.org

Participants:Coordinator Belgium Belgium Dr. Daniel Pipeleers, Dr. Harry Heimberg, Prof. Luc Bouwens, Vrije Universiteit Brussel tel: +32 2 477 45 41 fax: +32 2 477 45 45 daniel.pipeleers@vub.ac.be, Harry.Heimberg@vub.ac.be, lucbo@expa.vub.ac.be Frederic Lemaigre, Universite catholique de Louvain Bernard Peers, University of Liege Christel Hendrieckx, JDRF Center for Beta Cell Therapy in Europe, Brussels Zhidong Ling, Academic Hospital VUB, Brussels Andreas Jahraus, Beta-Cell NV, Zellik, SME Luc Marina Francois Schoonjans, Thromb-X NV, Louvain, SME Jens H. Nielsen, University of Copenhagen Finn Cilius Nielsen, Hospital Rigshospitalet, University of Copenhagen Ole D. Madsen & Palle Serup, Novo Nordisk A/S, Gentofte, IND Thomas Rolf Mandrup-Poulsen, Steno Diabetes Center, Gentofte Philippe Ravassard, Centre National de la Recherche Scientifique, Paris Raphael Scharfmann, Institut National de la Sante et de la Recherche Medicale, Paris Shimon Efrat, Tel Aviv University Fatima Bosch, Universitat Autonoma de Barcelona, Bellaterra (Cerdanyola del Valles) Jorge Ferrer, Hospital Clinic Provincial de Barcelona, Barcelona Henrik Semb, Lund University Johan Hyllner, Cell Therapeutics Scandinavia AB, Gothenburg, SME Pedro Luis Herrera, Faculte de Medecine, Universite de Geneve Anne Graphin-Botton, Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne Jonathan Michael Wyndham Slack, University of Bath Dominic John Withers, University College London

Denmark

France Israel Spain Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

SOFT TISSUE ENGINEERING FOR CONGENITAL BIRTH DEFECTS IN CHILDREN: NEW TREATMENT MODALITIES FOR SPINA BIFIDA, UROGENITAL AND ABDOMINAL WALL DEFECTSProposal acronym Contract n Duration (starting date) EuroSTEC LSHB-CT-2006-037409 5 years (01.01.07) EC contribution () Instrument Participants 7.828.500 IP 14

Abstract:The aim of this project is to use modern tissue engineering approaches to treat children with structural disorders present at birth, such as spina bifida, urogenital defects, gastroschisis, diaphragmatic hernia and esophageal atresia. The project strives to take a translational route through in vitro and animal experiments to early clinical trials. Tailor-made 'smart' biomatrices (scaffolds) will be prepared using natural scaffold molecules (collagen, elastin) and/or men-made polymers (poly lactic/glycolic acid), and will be substituted with regulatory molecules such as growth factors and glycosaminoglycans. A variety of cells, including stem cells, fibroblasts, muscle cells and urothelial/epithelial cells will be cultured in vitro and seeded into biomatrices. Biomatrices thus prepared, will be implanted using novel animal models for major congenital birth defects, and evaluated for their capacity to regenerate the correct tissues. Biomatrices will degrade in time and be replaced by the bodies own tissues thus assuring compliance with growth which is especially important in young children. Prenatal and postnatal reconstructive procedures will improve the final outcome of reconstructive surgery. Clinical trials for diaphragmatic hernias will form the start of the patient registry and protocol development for future clinical studies. Ethical and regulatory issues will be fully addressed before final clinical application, and parents and children will have to be able to understand these new treatment options. A dialogue with society, including patient's associations, will be sought. Demonstration activities will be undertaken to increase the awareness of new treatment modalities based on tissue-engineering. Finally, surgeons will be trained to use the new operation techniques. The project combines European leaders in the field of biomatrices, cell culture, animal models, surgery, and ethical and regulatory issues.

Web site:

not yet

Participants:Coordinator Netherlands Austria Belgium France Germany Netherlands Dr. Wouter Feitz, Department of Urology, Stichting Katholieke Universiteit, Radboud University Nijmegen Medical Centre, Nijmegen tel: +31-24-3613735 fax: +31-24-3541031 W.Feitz@uro.umcn.nl Amulya Saxena, Department of Paediatric Surgery, Medizinische Universitaet Graz (Medical University of Graz), Graz Jan Deprest, Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, Leuven Benjamin Herbage, Symatese Biomateriaux, Chaponost, IND Ingo Heschel, Research, Matricel GmbH, Herzogenrath, SME Gerard Barki, KARL STORZ GmbH & Co.KG, Tuttlingen, IND Paul Van den Berg, Department of Obstetrics and Gynaecology, University Medical Centre Groningen, Groningen Wim Witjes, Clinical Research, CuraTrial SMO & Research BV, Arnhem Noes De Vries, European Medical Contract Manufacturing, Nijmegen, SME Eduard Gratacos, Department of Obstetrics, Fetal Medicine and Therapy Research Group, Hospital Clinic, Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona Jons Hilborn, Department of Polymer Chemistry, Materials Chemistry, Uppsala University, Uppsala Peter Frey, Department of Pediatric Urology and Surgery, CHUV, and Integrative Bioscience Institute EPFL, Centre Hospitalier Universitaire Vaudois, Lausanne Andreas Zisch, Obstetrics, University Hospital Zurich, University Zurich, Zurich Kypros Nicolaides, Harris Birthright, Fetal Medicine Unit, King's College Hospital, The Fetal Medicine Foundation, London

Spain Sweden Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

CLINICAL EXPERIENCE WITH BONE MARROW CELLS AND MYOBLASTS TRANSPLANTATION FOR MYOCARDIAL REPAIRProposal acronym Contract n Duration (starting date) MYOCARDIAL REPAIR LSSM-CT-2004-511992 30 Months (01.01.05) EC contribution () Instrument Participants 400.000 SSA 9

Abstract:Heart failure caused by the ischaemic heart disease is one of the most common causes of morbidity an mortality across Europe, especially high among elderly people, but the post-infarction myocardial injury is also major cause of disability in younger survivors from myocardial infarction. The proposed project is dedicated to stimulate "state-of-the-art" research on the clinical applications of autologous stem cells, including bone marrow derived stem cells as well as myoblasts, to the regeneration of heart muscle in irreversibly damaged post-infarction regions. The consortium includes most experienced European clinical researchers in the field, which already had accomplished the phase I clinical trials in participating centres. The researchers from participating centres have agreed to coordinate their future clinical trials on stem cell transplantation for myocardial regeneration in patients with postinfarction heart failure, as a result of the proposed project. This will include analysis of polled clinical data obtained in participating centres, reciprocal exchange of information on cell culture and cell preparation for transplantation. This will also include standardization of clinical protocols aiming at evaluation of the clinical efficacy of myocardial replacement therapy as well as hand-on training of different techniques of cell delivery, including percutaneous cell transplantations, in particular trans-coronary arteries bone marrow stem cell delivery protocols as well as trans-ventricular and trans-cardiac-veins myoblast injection techniques. As a result of further integration of the consortium, it is expected to stimulate formation of a common future phase III studies at international level, especially with an option of submitting future Integrated Project application within the 6th Framework Programme.

Web site:

none

Participants:Coordinator Poland Czech Republic France Germany Lithuania Netherlands Poland Spain Prof. Tomasz Siminiak, University School of Medical Sciences, Department of Cardiology, District Hospital, Poznan tel: +48 618 212 422 fax: +48 618 212 319 tomasz.siminiak@usoms.poznan.pl Peter Widimsky, Charles University Prague, Cardiocenter Vinohrady, III Cardiology Clinic, Prague Phillipe Menasche, Hopital Europeen Georges Pompidou, Dept. of Cardiology, Paris Jean Ponsonnaille, University Hospital, Department of Cardiology, Region of Auvergne and University of Auvergne Medical Center, Clermont Ferrand Gustav Steinhoff, University of Rostock, FGKO, Klinik und Poliklinik fur Herzchirurgie, Rostock Vytautas Jonas Sirvydis, Vilnius University, Faculty of Medicine, Heart Surgery, Centre of Heart Clinic, Vilnius Patrick Serruys, Erasmus University Rotterdam, Thoraxcenter, Interventional Cardiology, Rotterdam Maciej Kurpisz, Polish Academy of Sciences, Institute of Human Genetics, Department of Reproductive Biology and Stem Cells, Poznan Francisco Fernandez-Aviles, Univ. Valladollid, Inst. de Ciencias Del Corazon, ICICOR, Valladolid

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases

FROM STEM CELL TECHNOLOGY TO FUNCTIONAL RESTORATION AFTER SPINAL CORD INJURYProposal acronym Contract n Duration (starting date) RESCUE LSHB-CT-2005-518233 3 years (01.12.2005) EC contribution () Instrument Participants 2.700.000 STREP 9

Abstract:Spinal cord injuries (SCI) have long been regarded as intractable, largely due to the alleged inability of the mammalian CMS to regenerate. However, over the last two decades, technological advances combined with the understanding of the pathophysiology of SCI have progressed to the point where it is now conceivable to develop therapeutic intervention strategies aimed at reconstructing the neuronal circuitry damaged by the lesion. One of the most powerful tools for this objective is based on stem cells, which can be used in three different ways to achieve this goal: 1) to bring permissive molecules and/or trophic agents at the level of the lesion to enhance the regenerative capacity of severed axons; 2) to use as replacement cells, grafted locally to stimulate specific circuits such as the central pattern generator (CPG); 3) to enhance the reparative potential of intrinsic stem cells. Most of the program will concentrate on human adult stem cells generated from bone marrow and adult CNS (including the spinal cord), but we will also consider foetal stem cells and established cell lines. Rodent cells will also be used as a model. This program will be achieved in three steps: Harvesting of adult and/or foetal stem cells (neural and non-neural), to be used directly or after transformation through genetic engineering. Grafting in the injured cord. Monitoring of the grafted cells with in vivo imaging, and assessing their effects using functional studies. It will require several technical prerequisites including standardisation for the harvesting of human stem cells, for the spinal cord lesion models, for the transplantation paradigms and for the functional studies. The final objective of the present project is the translation of experimental studies to clinical practice through the elaboration of a series of therapeutic tools to be used in a wide variety of clinical paradigms of SCI.

Web site:

not yet

Participants:Coordinator France Belgium Czech Republic France Prof. Alain Privat, INM, Institut National de la Sant et de la Recherche Mdicale, Montpellier tel: +33 499636006 fax: +33 499636020 privat@univ-montp2.fr Jean Schoenen, University of Lige, Lige Eva Sykova, Institute of Experimental Medicine ASCR, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague Jacques Mallet, Laboratoire de Gntique Molculaire de la Neurotransmission et des Processus Neurodgnratifs, Centre National de la Recherche Scientifique, Paris Manuel Gaviria, Neurva Inc., Montpellier, SME Aude Sirven, Inserm transfert, Paris Gary Anthony Brook, Rheinisch-Westflische Technische Hochschule for the faculty of medicine, University Hospital Aachen, Aachen Minerva Gimenez y Ribotta, Instituto de Neurociencias, Unit Neurobiology of Development, Lab. spinal cord pathology, Spanish National council for scientific research, Alicante Jack Price, Department of Neuroscience, King's College London, London

Germany Spain United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

APPLICATION AND PROCESS OPTIMIZATION OF HUMAN STEM CELLS FOR MYOCARDIUM REPAIRProposal acronym Contract n Duration (starting date) SC&CR LSHB-CT-2003-502988 3 years (01.02.04) EC contribution () Instrument Participants 1.954.200 STREP 10

Abstract:Myocardial infarction (Ml) is an irreversible injury where sudden interruption of blood flow caused by the occlusion of an artery leads quickly to cardiac myocytes death, loss of tissue and scar formation. Since the self-renewal ability of adult cardiac myocytes is limited, the development of strategies to regenerate damaged myocardium and improve its function represents a major challenge in the treatment of cardiac diseases. Recent evidences have suggested that multipotent somatic stem cells can become reprogrammed in new tissue-specific stem cell niches. However, despite the growing number of observations reporting "trans-differentiation" of adult tissue-derived stem cells, there are no conclusive evidences on the mechanism(s) underlying changes in stem cell fate and sufficient information on the therapeutic potential of these cells. In this proposal we aim to provide a contribution on validation of the use of adult tissue derived stem cells for myocardial repair by: 1) identifying the most suitable adult stem cell type(s) to be used to promote myocardial repair/regeneration; 2) unraveling the combination of stimuli that might drive differentiation of stem cells toward a cardiac myocyte lineage; 3) define genes and factors driving stem cell differentiation into cardiac lineage and set-up safe and effective vectors and protocols to induce cardiac myocyte differentiation pathway(s) by gene transfer; 4) assessing the functional properties of stem cell-derived cardiac myocytes; 5) unraveling the action of factors that might be involved in recruitment and homing of endogenous stem cell in myocardium; 6) evaluating the mid- and long-term effects of stem cell administration by clinical trials of autologous hematopoietic stem cell administration in patients suffering ischemic heart disease.

Web site:

http://www.sc-cr.org

Participants:Coordinator Italy Germany Italy Dr. Maurizio Capogrossi Colognesi, Provincia Italiana della Congregazione dei Figli dell'Immacolata Concezione - Istituto Dermopatico dell'Immacolata, Rome tel: +39 06 6646 2433 fax: +39 06 6646 2430 capogrossi@idi.it Anna Wobus, Institute of Plant Genetics and Crop Plant Research, Gatersleben Carsten Werner, Institut fr Polymerforschung Dresden e V, Dept. Biokompatible Materialien Michael Hallek, Gene Center, Ludwigs-Maximilians-University of Munich Maurizio Pesce, Centro Cardiologico Monzino, Milan Antonio Zaza, Universit degli Studi Milano-Bicocca Nadia Rosenthal, European Molecular Biology Laboratory, Monterotondo Scalo Luigi Cavenaghi, Areta International, Milan, SME Jacques De Bakker, Interuniversity Cardiology Institute of the Netherlands, Utrecht

Netherlands Poland

Aldona Dembinska-Kec, The Jagiellonian University, Medical College, Krakow

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

TOWARDS A STEM CELL THERAPY FOR STROKEProposal acronym Contract n Duration (starting date) STEMSTROKE LSHB-CT-2006-037187 3 years (01.01.07) EC contribution () Instrument Participants 2.475.508 STREP 6

Abstract:Stroke is a major cause of long-term disability in humans, but effective treatments are lacking. The StemStroke consortium comprises 5 highly qualified academic research teams and one SME which, together with excellent clinicians in the stroke field, will perform innovative research leading to the first preclinical protocol for application of stem cell therapy in stroke patients. Human neural stem cell (NSC) lines will be isolated from the foetal and adult brain, and from embryonic stem cells. Cellular and molecular mechanisms regulating the proliferation, migration, survival, and differentiation of the NSC lines after transplantation into the stroke-damaged rodent brain will be determined. In parallel, StemStroke will unravel mechanisms regulating self-repair after stroke through formation of new neurons from the adult brain's own NSCs. The StemStroke will explore the morphological and functional integration of grafted and endogenously generated NSCs and their progeny in the stroke-damaged brain, and develop new in vivo imaging and behavioural tests, relevant for the human situation, for assessment of stem cell function and recovery of sensory, motor and cognitive deficits. Finally, StemStroke will optimize transplantation- and endogenous neurogenesis-based strategies and create an important preclinical protocol which can be rapidly translated into human trials. The teams contain top-level expertise in animal models of stroke and MRI-based in vivo imaging, stem cell, molecular, and cellular biology, molecular genetics, animal behaviour and psychology, translational research, and clinical cell therapy. Through the participating SME, commercial exploitation of the knowledge emerging from the project is ensured. The complementarity of expertise within the consortium, together with the intellectual and technological resources available from each partner, will ensure efficient and high-quality performance and feasibility of achieving its ambitious S&T goals.

Web site:

not yet

Participants:Coordinator Sweden Germany Sweden United Kingdom Prof. Zaal Kokaia, Clinical Neuroscience, Faculty of Medicine, Stem Cell Center University Hospital, Lund University, Lund tel: +46 462220276 fax: +46 462220560 Zaal.Kokaia@med.lu.se Mathias Hoehn, In-vivo-NMR-Laboratory, Max-Planck-Institut fr neurologische Forschung, Kln Liliana Minichiello, EMBL-Mouse Biology Unit, EMBL-Monterotondo, European Molecular Biology Laboratory (Monterotondo-Rome), Heidelberg Lilian Wikstrm, NeuroNova AB, Stockholm, SME Austin Smith, Institute For Stem Cell Biology, The Chancellor, Master, and Scholars of the University of Cambridge, Cambridge Stephen Dunnett, School of Biosciences, Cardif University, Cardiff

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

MULTIPOTENT ADULT PROGENITOR CELLS TO TREAT STROKEProposal acronym Contract n Duration (starting date) STROKEMAP LSHB-CT-2006-037186 3 years (01.10.06) EC contribution () Instrument Participants 2.400.000 STREP 8

Abstract:Successful therapy for stroke will be achieved using cells that can limit ischemic injury and differentiate into the multiple cell types needed for restoring blood flow and neural circuits, and would be available for therapy 'off the shelf. As Multipotent Adult Progenitor Cells (MAPCs) differentiate into vascular and neural cells, and reconstitute damaged tissues in vivo, we hypothesize that MAPCs is an ideal allogeneic cell product to treat stroke. In WP1, WP2 and WP3, we will develop approaches to generate committed vascular cells and neuroprogenitors, and identify key molecular events that guide differentiation. WPs 4-7 will rigorously evaluate the pre-clinical efficacy of allogeneic MAPCs or their progeny in stroke. This will include development of noninvasive imaging techniques to follow the fate of grafted cells and evaluate their impact on CNS function (WP4). We will compare the efficacy of MAPCs with that of till now gold-standard stem cell populations in stroke, and determine mechanisms underlying observed effects (WP5). We will examine the immunogenicity of MAPCs and their differentiated progeny in vitro (WP6) and in vivo using mice with a 'human immune system' (WP7). Studies in WP9 will develop clinical grade culture systems to generate human MAPCs and, if needed, lineage committed progeny. Studies in WP8 will develop a framework in which to develop clinical grade stem cell products in an ethically responsible manner. Specific attention to the management of the project. The management, exploitation and dissemination of the project will be ensured through WP10. These studies will lay the foundation for clinical trials of MAPCs in stroke in Europe in subsequent years. The highly innovative methods, tools and technologies that will be developed will not only be applicable in the area of stem cell based therapies for stroke, but may significantly advance use of human stem cells in regenerative medicine.

Web site:

not yet

Participants:Coordinator Belgium Prof. Catherine Verfaillie, Department Oncology - Hematology Transplantation, Katholieke Universiteit Leuven, Leuven, Leuven, BE, BE, Belgium, N, HE, PNP, +32 16 34 68 95, +32 16 34, Catherine.Verfaillie@med.kuleuven.be tel: +31 71 52 66 639 fax: +31 71 52 48 158 p.c.w.hogendoorn@lumc.nl Peter Carmeliet, Center for Transgene Technology and Gene Therapy, Vlaams Interuniversitair Instituut voor Biotechnologie, Leuven Gil Van Bokkelen, ReGenesys, Brussels, SME Jean-Marc Idee, Research Department, Guerbet, Roissy Charles de Gaulle, IND Felipe Prosper Cardoso, University Clinic of Navarra - Dept. of Hematology, University of Navarra, Pamplona Jose Manuel Garcia Verdugo, Dept. Neurobiologia Comparada Instituto Cavanilles, Universitat de Valncia. Estudi General, Paterna Ernest Arenas, Dept. of Medical Biochemistry and Biophysics, Divsion of Molecular Neurobiology, Karolinska Institutet, Stockholm Markus G. Manz, Institute For Research in Biomedicine, Institute for Research in Biomedicine, Bellinzona

Belgium France Spain

Sweden Switzerland

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

EX VIVO GENE THERAPY FOR RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA : PRE-CLINICAL AND CLINICAL STUDIESProposal acronym Contract n Duration (starting date) THERAPEUSKIN LSHB-CT-2005-511974 3 years (01.07.05) EC contribution () Instrument Participants 1.523.000 STREP 9

Abstract:We aim to develop ex vivo gene therapy of recessive dystrophic epidermolysis bullosa (RDEB, #OMIM 226600, *120120). RDEB is caused by loss of function mutations in the collagen VII gene (COL7A1) encoding anchoring fibrils. It is one of the most severe genodermatoses in children and adults. The patients suffer from skin blistering since birth, and from severe local and systemic complications resulting in poor prognosis. We lack a specific treatment for RDEB, but ex vivo gene transfer to epidermal stem cells shows therapeutic potential. We and others have shown in vitro correction of primary RDEB keratinocytes by retroviral and lentivirat COL7A1 cDNA vectors Reports of leukemia caused by retroviral insertional mutagenesis in gene therapy of X-SCID steered us toward safer, 'Self Inactivating (SIN)' vectors. In Step I of this project, we will design safe SIN retroviral and lentiviral COL7A1 vectors. Different promoters and viral envelope proteins will be tested for efficient gene delivery and expression in cultured primary keratinocytes and fibroblasts. We will study the proliferate capacity of transduced cells, assess long-term expression of recombinant collagen VII, and analyse proviral integration sites for deleterious effects. We will analyse synthesis, folding and secretion of recombinant collagen VII, and its ability to form anchoring fibres in a skin equivalent model and in skin grafts on mice. Vectors will be constructed and produced with full traceability to Good Laboratory Practice (GLP) standards. In Step II, cell clones producing the highest titres of the selected SIN retroviral or lentiviral vector (mini-cell bank} will be expanded, evaluated, and a unique GMP master cell bank (MCB) will be established This MCB will be tested for safety, to be used in the production of clinical grade viral particles. Step III will be a pilot clinical trial (Phase I/II) of genetically corrected autologous skin grafts in selected patients. This project, which combines the complementary expertise of several international groups, will serve as proof of principle for the treatment of RDEB, and as a model for the treatment of severe dermatological genetic disorders by ex vivo gene therapy.

Web site:

http://www.debra-international.org/researche2.htm

Participants:Coordinator France France Germany Switzerland United Kingdom Prof. Alain Hovnanian, Institut National de la Sante et de la Recherche Medicale, Toulouse tel: +33 5 61 77 90 79 fax: +33 5 62 74 83 50 Alain.Hovnanian@toulouse.inserm.fr Christine Bodemer, Centre Hospitalo-Univ. Necker Enfants Malades (Assistance Publique), Paris Olivier Danos, Genethon, Evry Jonathan Dando, INSERM Transfert SA, Paris Luis Moroder, Max Planck Society for the Advancement of Sciences, represented by MPI of Biochemistry, Martinsried Yann Barrandon, Ecole Polytechnique Federale de Lausanne Irene May Leigh, Queen Mary & Westfield College, University of London John Alexander McGrath, Kings College London, University of London John Richard William Dart, DEBRA Europe, Crowthorne

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

GENE TRANSFER IN SKIN EQUIVALENTS AND STEM CELLS: NOVEL STRATEGIES FOR CHRONIC ULCER REPAIR AND TISSUE REGENERATIONProposal acronym Contract n Duration (starting date) Ulcer Therapy LSHB-CT-2005-512102 3 years (01.08.05) EC contribution () Instrument Participants 2.392.000 STREP 8

Abstract:Chronic ulcers and defective tissue repair represent a major health problem. Conventional therapeutic approaches are not sufficient to guarantee an adequate healing in chronic ulcers and recurrence is frequent. Among non conventional treatments, short protein half-life and inefficient delivery to target cells have been identified as main limitations of the topical application of recombinant growth factors. Similarly, the therapeutic effect of skin equivalent grafting was limited, in particular due to impaired production of granulation tissue by the host. The present project relays on the development and validation of novel therapeutic strategies for tissue regeneration, based on the use of genetically modified stem cells and skin equivalents. The plan structure starts with a multidisciplinary research approach aimed at characterising the role and mechanism of action of potentially therapeutic proteins. In parallel, a wide analysis will be conducted to exploit the most suitable adeno and adeno-associated viral vectors for gene transfer into selected cell types. The research will be then translated towards in vivo application of genetically modified stem cells and skin equivalents, as delivery systems of therapeutic proteins. The pathology chosen to validate these innovative therapeutic strategies is the impaired wound healing, due to diabetes. The potential therapeutic effect of ex-vivo engineered skin equivalents and bone marrow-derived stem cells will be therefore tested at first on diabetic animals, or other animal models of impaired wound healing. A Phase I clinical trial of diabetic chronic ulcers, with autologous skin equivalents ex-vivo engineered to over-express nerve growth factor as a therapeutic protein, will be then accomplished.

Web site:

not yet

Participants:Coordinator Italy Germany Italy Spain Switzerland Prof. Jrgen Hescheler, Universitt Kln tel: +49 221 478 737 3 fax: +49 221 478 383 34 j.hescheler@uni-koeln.de Michael Hallek, Gene Center, Inst. for Biochemistry of the Ludwigs-Maximilians Univ. of Munich Sabine Eming, Depart. of Dermatology, University of Cologne Maurizio Pesce, Centro Cardiologico Monzino - IRCCS, Milan Nadia Rosenthal, European Molecular Biology Laboratory, Monterotondo Scalo (RM) Elena Dellambra, IDI FARMACEUTICI SpA, Pomezia (RM), SME Jose Luis Jorcano Noval, Centro de investigaciones energeticas medioambientales y tecnologicas, Madrid Sabine Werner, Swiss Federal Institute of Technology, Zurich

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

TREATING Improvement of standard hematopoietic stem cell transplantation

41

THE DEVELOPMENT OF IMMUNOTHERAPEUTIC STRATEGIES TO TREAT HAEMATOLOGICAL AND NEOPLASTIC DISEASES ON THE BASIS OF OPTIMISED ALLOGENEIC STEM CELL TRANSPLANTATIONProposal acronym Contract n Duration (starting date) ALLOSTEM LSHB-CT-2004-503319 3.5 years (01.05.04) EC contribution () Instrument Participants 8.000.000 IP 27

Abstract:Haematological disease, either malignant or otherwise, carries a significant burden of morbidity and mortality. Recent advances in mapping and sequencing of the human genome make possible an approach to the treatment of these diseases which exploits the genetic differences between individuals to produce targets through which the immune system can eliminate the diseased cells. In practice this process of immunotherapy involves an allogeneic haematopoetic stem cell transplant, with subsequent delivery of specific immune effector cells expanded from the donor. The AlloStem project brings together clinical and research groups from across the EU who individually are amongst the world leaders in the field of immunotherapy to coordinate and complement their efforts into a unified and directed program. We will develop new protocols for the treatment of patients with haematological disease and for the effective delivery of immunogenomicsbased therapies. The end results of the project will be both an improvement in the health care for EU citizens and the development of new genome-based pharmaceuticals that can be exploited worldwide.

Web site:

http://www.allostem.org

Participants:Coordinator United Kingdom Argentina Brazil Czech Republic France Prof. Alejandro Madrigal, The Anthony Nolan Trust, London tel: +44 207 28 48 315 fax: +44 207 28 48 331 madrigal@rfc.ucl.ac.uk Javier Bordone, ITMO-Fundacin Mainetti, Gonnet Ricardo Pasquini, Hospital de Clinicas, Universidade Federal do Paran, Curitiba Jirina Bartunkova, Charles University Prague Dominique Charron, HLA et MEDECINE , Paris Franois Romagne, Innate Pharma SAS, Marseille, SME Eric Vivier, Centre National de la Recherche Scientifique, Marseille Laurence Zitvogel, Institut Gustave Roussy, Villejuif Hermann Einsele, Eberhard Karls Universitt Tbingen Mario Assenmacher, Miltenyi Biotec GmbH, Bergish-Gladbach, IND Hans-Georg Rammensee, Eberhard-Karls-Universitaet Tuebingen Dolores J. Schendel, GSF Nat. Research Center for the Environment and Health, Neuherberg Yair Reisner, Weizmann Institute of Science, Rehovot Head Locatelli, IRCCS Policlinico San Matteo, Pavia Alessandro Moretta, University of Genova Lorenzo Moretta, Istituto Giannina Gaslini, Genova Andrea Velardi, University of Perugia Johan Herman Frederik Falkenburg, Leiden University Medical Center

Germany

Israel Italy

Netherlands Poland Russian Federation Spain Sweden United Kingdom

Andrzej Lange, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw Leonid Alexeev, State Research Center, Moscow Manuel-Nicolas Fernandez, Universidad Autonoma de Madrid Joan Garcia, Centro de Transfusio Banc de Teixits, Barcelona Pavel Pisa, Karolinska institutet, Stockholm Alejandro Madrigal, AlloStem, London, SME Peter Michael Maguire, Dynal Biotech Ltd , Bromborough, SME Nikolai Schwabe, PROIMMUNE Limited, Oxford, SME Robert Charles Rees, Nottingham Trent University

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

FACILITATING INTERNATIONAL PROSPECTIVE CLINICAL TRIALS IN STEM CELL TRANSPLANTATIONProposal acronym Contract n Duration (starting date) CLINT LSSB-CT-2007-037662 2 years (01.04.07) EC contribution () Instrument Participants 500.000 SSA 4

Abstract:Stem cell transplantation (SCT) is the treatment of choice for many blood diseases. Within healthcare provision, SCT is one of the most costly and one of the most risky procedures for patients with transplant related mortalities of up to 50%. SCT remains on the cutting edge of translational medicine and recently there have been many changes in the way in transplant methodology such as the introduction of new drugs and technologies. These innovations have the potential to improve patient outcome but also to increase the cost considerably. At the same time there are many new developments with respect to targeted drug therapies and supportive care in these diseases which may replace or delay transplant for some patients. These new therapies are also expensive and require urgent evaluation. It is essential that they and SCT are used wisely and economically. The SCT community is always prepared to critically evaluate the role of transplant, as is exemplified by the transmission of outcome data from individual centres to a central database held by the European Transplant Group (EBMT) for further analysis and reporting. SCT physicians have also been enthusiastic exponents of clinical trials and are ready to test new hypotheses and to compare SCT with other treatments. Their ability to do this has been severely curtailed by the recent requirements imposed by the EU Directive on Clinical Trials. Although introduced with laudable intentions the effect of the Directive has been to increase the resources and therefore the expense of clinical trials whilst at the same time national differences in interpretation of the new legislation has rendered international studies very difficult. The objective of this SSA is to support the EBMT to further develop the infrastructure necessary to perform academically initiated international prospective studies in SCT throughout Europe. This will hasten the evaluation of new treatment strategies and improve the outcome for European citizens.

Web site:

not yet

Participants:Coordinator United Kingdom Netherlands United Kingdom United States Prof. Jane Apperley, Department of Haematology, Division of Investigative Sciences, Imperial College of Science, Medicine and Technology, London tel: +44 20 8383 3237 fax: +44 20 8742 9335 j.apperley@imperial.ac.uk Harry Schouten, University Hospital Maastricht, Dept. Internal Med. Hematology / Oncology, European Group for Blood and Marrow Transplantation, Maastricht Doris Schroeder, Centre for Professional Ethics, University of Central Lancashire, Preston Mary Horowitz, CIBMTR, Medical College of Wisconsin Center for International Blood and Marrow Transplant Research, Milwaukee

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

STRENGTHEN AND DEVELOP SCIENTIFIC AND TECHNOLOGICAL EXCELLENCE IN RESEARCH AND THERAPY OF LEUKEMIA (CML, AML, MDS, CLL, ADULT ALL) BY COOPERATION AND INTEGRATION OF THE LEADING NATIONAL LEUKEMIA NETProposal acronym Contract n Duration (starting date) EUROPEAN LEUKEMIANET LSHC-CT-2004-503216 5 years (01.09.04) EC contribution () Instrument Participants 6.000.000 NoE 116

Abstract:Leukemias are a challenge to society and a cost factor because of their frequency in all age groups. They also serve as a model for a variety of diseases and possess exemplary relevance for basic research and patient care. Leukemia research and therapy have achieved high standards and even a leading position in several European countries with regard to clinical trials, standardisation of diagnostics and molecular studies of signal transduction and gene expression. A true European world leadership, however, has not been accomplished yet due to national fragmentation of leukemia trial groups, diagnostic approaches and treatment research activities and a need for central information and communication structures. The objective is to integrate the leading leukemia trial groups (CML, AML, ALL, CLL, MDS, CMPD), their interdisciplinary partners (diagnostics, treatment research, registry, guidelines), industry and SMEs across Europe form a European cooperative network for advancements in leukemia-related research and health care. Integration will be supported by central information, communication, education and management structures. The main goals are to intensify target and drug discovery, to shorten the time period to clinical translation, to apply advanced genomics, telematics and biotechnology to therapeutic progress and to promote translational research relevant also for solid cancers by large clinical trials. Furthermore, metanalyses of specific subaspects,elaboration of prognostic scores, recognition of gender specific differences, creation of uniform data sets for trials and registration, introduction of standards for diagnostics and treatment procedures and development of evidence based guidelines will be promoted throughout Europe. The proposed network will have the expertise and critical mass for European added value and world leadership. It will structure European research durably, spread European scientific excellence in the field of leukemias and can start immediately.

Web site:

http://www.leukemia-net.org

Participants:Coordinator Germany Austria Prof. Rudiger Hehlmann, Ruprecht-Karls-Universitt Heidelberg tel: +49 621 383 411 5 fax: +49 621 383 420 1 R.Hehlmann@urz.uni-heidelberg.de Gnther Gell, Institut f. Med. Informatik, Statistik u. Dokumentation, Universitat Graz Josef Thaler, Allg. . Krankenhaus der Barmherzigen Schwestern vom heiligen Kreuz, Wels Christa Fonatsch, Medizinische Universitt Wien Oskar Haas, Children's Cancer Research Institute, Vienna Heinz Zwierzina, Universitt Innsbruck Anne Hagemeijer, Katholieke Universiteit Leuven Philippe Martiat, Institut Jules Bordet, Universit libre de Bruxelles Labar Boris, University Hospital Center, Zagreb

Belgium Croatia Czech Republic Denmark Finland France

Jiri Mayer, The Brno Faculty Hospital Peter Hokland, Aarhus University Hospital Christian Geisler, HS Rigshospitalet, Copenhage Hans Hasselbalch, Odense University Hospital Tapani Ruutu, Helsinki University Central Hospital Sakari Knuutila, University of Helsinki Jean-Loup Huret, Universit de Poitiers Franois-Xavier Mahon, Universit Victor Segalen, Bordeaux Pierre Fenaux, Hopital Avicenne, Bobigny Jean-Pierre Marie, Universit Pierre et Marie Curie, Paris Laurent Degos, Institut universitaire d'hmatologie, Hpital St. Louis, Paris Norbert Ifrah, University of Angers Guillaume Dighiero, Institut Pasteur, Paris Xavier Troussard, Centre hospitalier universitaire de Caen Claude Preudhomme, Centre hospitalier rgional universitaire de Lille Marie-Caroline Le Bousse-Kerdils, Institut national de la sant et de la recherche mdicale, Villejuif Marie-Christine Bn, Universit Henri Poincar, Nancy Eliane Glickman, Association pour la recherche sur les transplantations mdullaires, Paris Catherine Cordonnier, Assistance publique-Hpitaux de Paris, Crteil Nicole Dastugue, Htel-Dieu Saint Jaques, Centre hospitalier universitaire de Toulouse Fabienne Hermite, Ipsogen SAS, Marseille, SME

Germany

Hungary Ireland Israel

Dieter Hoelzer, University of Frankfurt Ulrike Holtkamp, Deutsche Leukamie und Lymphom-Hilfe e.V., Bonn Karl berla, Ludwig-Maximilians-University Munich Wolfgang Berdel, University of Muenster Hartmut Dhner, University Hospital Ulm Gerhard Ehninger, University Hospital Carl Gustav Carus, Technical University Dresden Hans Heinrich Kreipe, Medizinische Hochschule Hannover Dietger Niederwieser, Universitatsklinikum Leipzig Carlo Aul, St. Johannes Hospital Duisburg Norbert Gattermann, Universittsklinikum Dsseldorf Michael Hallek, University of Cologne Andrew J. Ullmann, Johannes Gutenberg-Universitat, Mainz Annette Schmitt-Grff, Universittsklinikum Freiburg Winfried Gassmann, St.Marien-Krankenhaus Siegen gem. GmbH, Siegen Wolf-Dieter Ludwig, Charit - Universittsmedizin, Berlin Harald Rieder, Philipps-University, Marburg Jochen Harbott, Children's University Hospital, Justus-Liebig-Universitat, Giessen Michael Kneba, University Hospital Schleswig-Holstein, Kiel Lothar Kanz, Eberhard Karls Universitat, Tubingen Justus Duyster, Technical University of Munich Walter Fiedler, Universittsklinikum Hamburg-Eppendorf Einsele Hermann, Bayerische Julius-Maximilians-Universitt, Wrzburg Tamas Masszi, St. Laszlo Hospital, Budapest

Michael ODwyer, University College Hospital Galway Jacob Rowe, Fund for Medical Research Development of Infrastructure and Health Services, Rambam Medical Center, Haifa Alexander Levitzki, The Hebrew University of Jerusalem Nurit Livnah, Peptor LTD, Rehovot Gina Zini, Catholic University of Sacred Heart, Rome Michele Baccarani, University of Bologna Giuseppe Saglio, Universit degli Studi di Torino Sergio Amadori, Universit degli Studi di Roma Tor Vergara Roberto Fo, University "La Sapienza" of Rome Tiziano Barbui, Ospedali Riuniti Di Bergamo Federico Caligaris-Cappio, Universit Vita-Salute San Raffaele, Milan Carlo Bernasconi, Fondazione Collegio Ghislieri, Pavia Giovanni Barosi, IRCCS Policlinico San Matteo, Pavia Francesco Frassoni, Azienda Ospedaliera Ospedale San Martino, Genova Cristina Mecucci, University of Perugia Mariano Rocchi, Universit degli Studi di Bari Paolo Bernasconi, Universit degli Studi di Pavia Fabrizio Pane, CEINGE Biotecnologie avanzate SCARL, Napoli Giuseppe Basso, Universit degli studi di Padova Sergio Ferrari, University of Modena and Reggio Emilia, Modena Anna Locasciulli, Azienda Ospedaliera San Camillo Forlanini, Roma Claudio Viscoli, University of Genova Jacques van Dongen, Erasmus University Medical Center, Rotterdam Theo De Witte, Stichting Katholieke Universiteit, University Medical Centre Nijmegen G. J. Ossenkoppele, VU Academic Medical Center, Amsterdam A.W. Dekker, University Medical Center, Utrecht Marinus Van Oers, Academisch Ziekenhuis bij de Universiteit van Amsterdam Roelof Willemze, Leiden University Medical Center Andrzej Hellmann, Medical University of Gdansk Aleksander Skotnicki, Jagiellonian University, Medical College, Krakow Jerzy Holowiecki, Medical University of Silesia, Katowice Jan Walewski, The Maria Sklodowska-Curie Memorial Cancer Center, Warsaw Tadeusz Robak, Uniwersytet Medyczny w Lodzi, Lodz Wieslaw Wiktor Jedrzejczak, Medical University of Warsaw Nicolae-Dan Colita, Fundeni Clinical Institute, Bucharest Valery Savchenko, National Research Center for Hematology, Moscow Emili Montserrat, University of Barcelona Juan Luis Steegmann, Hospital Universitario de la Princesa, Madrid Miguel Sanz, Fundacin Hospital Universitario "La Fe", Valencia Jorge Sierra, Hospital de Sant Pau, Barcelona Jos Maria Ribera, Hospital Universitari Germans Trias i Pujol, Badalona Alberto Orfao, Universidad de Salamanca Jess M. Hernndez, Fundacin de Investigacin del Cncer de la Universidad de Salamanca

Italy

Netherlands

Poland

Romania Russia Spain

Sweden

Switzerland Turkey United Kingdom

Bengt Simonsson, University Hospital Uppsala Per Ljungman, Karolinska Institutet, Stockholm Bertil Hohansson, Lunds Universitet Mats Brune, Gteborg University Alois Gratwohl, University Hospitals, Basel Andreas Tobler, University of Bern Martine Jotterand, Centre Hospitalier Universitaire Vaudois, Lausanne Ibrahim Haznedaroglu, Ankara University Stephen OBrien, University of Newcastle upon Tyne Alan Burnett, University of Wales College of Medicine, Cardiff Estella Matutes, Institute of Cancer Research, London David Oscier, Royal Bournemouth Hospital John Goldman, Imperial College of Science, Medicine and Technology, London David Bowen, University of Dundee Ghulam Jeelani Mufti, King's College London Debra Mia Lillington, Queen Mary & Westfield College, London Nicholas Cross, University of Southampton John Reilly, The University of Sheffield Khalid Tobal, Central Manchester and Manchester Children's University Hospitals Rolf Apweiler, European Molecular Biology Laboratory, EBI, Cambridge Katherine Ward, University College London

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer sector

FURTHER IMPROVEMENT OF RADIOTHERAPY OF CANCER THROUGH SIDE EFFECT REDUCTION BY APPLICATION OF ADULT STEM CELL THERAPYProposal acronym Contract n Duration (starting date) FIRST LSHC-CT-2004-503436 2 years (01.09.04) EC contribution () Instrument Participants 1.500.000 IP 8

Abstract:Radiotherapy is the second most important treatment modality after surgery in the treatment of cancer. At present over 50% of all cancer patients receive radiotherapy at one stage in their course. Inevitably normal tissues are also exposed to ionising radiation during radiotherapy of tumours. This can result in organ failure and hence seriously can limit the treatment dose. Reduction of the side effects of radiotherapy will not only increase the quality of life after the treatment and but may also result in increased survival of cancer patients as it will allow dose-escalation to the tumour. This is true even if the most optimal physical dose-delivery (conformal therapy, protons) of radiation is applied. Radiation-induced (late) organ failure is mainly caused by stem cell sterilisation, leading to a reduced reconstitution of functional cells. Replenishment of the depleted stem cell compartment should allow regeneration of irradiated tissues. Multipotent stem cells have now been shown to reside in multiple adult tissues. For stem cell therapy purposes cells obtained from easy accessible places as e.g. the skin and from bone marrow or peripheral blood appear ideal. The innovative vision of this project is to reduce radiation-induced complications through stem cell therapy. Hereto, 1) tissue specific adult stem cells will be isolated, characterised and expanded, 2) non-specific bone marrow derived stem cells will be generated, mobilised, characterised and expanded 3) thus obtained stem cells will be tested for their capability to ameliorate radiation-induced complications in organs affected by radiotherapy 4) and potential risks will be assessed. A successful replacement of stem cells and subsequent amelioration of radiation-induced complications may open the road to completely new strategies in radiotherapy and help combating cancer.

Web site:

http://www.euproject-first.org

Participants:Coordinator Netherlands Denmark France Germany Netherlands United Kingdom Dr Robert Coppes, University of Groningen tel: +31 50 363 27 09 fax: +31 50 363 29 13 r.p.coppes@med.rug.nl Thue W. Schwartz, 7TM Pharma A/S, Hoersholm, IND Michle Martin, Commissariat l'Energie Atomique, Paris Pierre Charbord, Universit Franois Rabelais, Tours Dominique Pierre Thierry, Institut Radioprotection et Suret Nuclaire, Fontenay-aux-roses Wolfgang Drr, University of Technology, Dresden

Jan Wondergem, Leiden University Medical Center Mohi Rezvani, Chancellor Masters and Scholars of the University of Oxford

Commission: Directorate General for Research - Health Directorate - Unit F2 Major Diseases Cancer Sector

REPROGRAMMING THE IMMUNE SYSTEM FOR THE ESTABLISHMENT OF TOLERANCEProposal acronym Contract n Duration (starting date) RISET LSHB-CT-2004-512087 5 Years (01.03.05) EC contribution () Instrument Participants 10.000.000 IP 22

Abstract:Transplantation dramatically improves the survival of patients with end-stage failure of vital organs. However, as a direct consequence of the immunosuppressive drugs permanently required to prevent rejection, recipients have a significantly increased risk of infection and malignancies Moreover, these drugs are expensive, do not prevent long-term damage of the graft, and exert toxic effects outside the immune system. The induction of transplant tolerance, defined as permanent acceptance of the graft in absence of continuous immunosuppression, would be a major step forward Recent advances in post-genomic immunology suggest that this goal is achievable in a near future. Indeed, new biotechnology products have been shown to promote long-term transplant acceptance in pre-clinical models. RISET will focus on the translation of these advances into industrial development and clinical practice First, diagnostic tests to identify transplanted patients for whom immunosuppressive treatment could be safely minimized or withdrawn will be developed. These tests will be applied to patients under conventional treatment as well as to patients enrolled in pilot clinical investigations based on cellular products with potential for tolerance induction. Because of the nature of this research, effective communication with patient organizations and regulatory bodies will be organized, and related ethical and societal questions will be specifically addressed. In parallel, relevant models of tolerance will be used to identify new genes, molecules or cell types that will form the basis for novel diagnostics and therapeutic approaches. The exploitation of the knowledge created in RISET will be facilitated by the inclusion of several SMEs in the consortium and the creation of an industrial platform. In order to exploit innovative concepts emerging outside the consortium, RISET will be open to new industrial or academic partners for which a budget has been provisioned.

Web site:

http://www.risetfp6.org

Participants:Coordinator Belgium Belgium Czech Republic France Prof. Michel Goldman, Departement Immunologie Experimentale, Universite Libre de Bruxelles tel: +32 25556138 fax: +32 25556914 mgoldman@ulb.ac.be Anne-Marie Priells, Tech-Know Consultants SPRL, Koksijde, Waterloo, SME Jiri Lacha, Department of Nephrology, Transplantcentre IKEM, Transplant Laboratory, Centre of Experimental Medicine IKEM, lnstitute for Clinical and Experimental Medicine, Prague Marina Guillet, TcLand, Nantes, SME Lucienne Chatenoud, Laboratoire d'Immunologie Biologie - UFR Necker Enfants Malades Hopital Necker Enfants Malades, Universite Rene Descartes, Paris Anne Cambon-Thomsen, lnserm U 558 - Epidemiologie et analyses en sante publique, Faculte de Medecine, lnstitut National de la Sante et de la Recherche Medicale, Toulouse Jean-Paul Soulillou, INSERM U437 / ITERT, Centre Hospitalier de Nantes, Nantes Uwe Janssen, Memorec Biotec GmbH, Cologne, IND Ulrich Kunzendorf, Division of Nephrology & Hypertension, University of Schleswig-Holstein, Kiel Albrecht Wendel, Steinbeis Technology, Transfer Center for ln-vitro Pharmacology & Toxicology, Konstanz, SME Fred Faendrich, Dept. of General and Thoracic Surgery, University of Schleswig-Holstein, BLASTICON GmbH Biotechnology Company, Kiel, IND Hans-Dieter Volk, Dept of Medical Immunology, Charit Universittsmedizin Berlin, Berlin Bernd Arnold, Tumor lmmunology / Molecular lmmunology, Deutsches Krebsforschungszentrum, Heidelberg Yair Reisner, lmmunology-Biology, Weizmann lnstitute of Science, Rehovot Maria Grazia Roncarolo, Hsr-Tiget, Fondazione Centro San Raffaele Del Monte Tabor, Milan Luciano Adorini, Bioxell S.P.A., Milano Mohamed R. Daha, Department of Nephrology, Leiden University Medical Center, Leiden Blanca Miranda Serrano, National Transplant Coordination, Organizacin Nacional de Trasplantes, Madrid Robert Rieben, Department of Clinical Research, Cardiology, University of Bern Hospital, Bern Kathryn Jayne Wood, Nuffield Department of Surgery, Masters & Scholars of the University of Oxford Herman Waldmann, Sir William Dunn School of Pathology, University of Oxford Robert Lechler, Department of lmmunology, Faculty of Medicine, lmperial College London, London

Germany

Israel Italy Netherlands Spain Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

THE DEVELOPMENT OF NEW DIAGNOSTIC TESTS, NEW TOOLS AND NONINVASIVE METHODS FOR THE PREVENTION, EARLY DIAGNOSIS AND MONITORING FOR HAEMATOPOIETIC STEM CELL TRANSPLANTATIONProposal acronym Contract n Duration (starting date) STEMDIAGNOSTICS LSHB-CT-2007-037703 3 years (01.04.07) EC contribution () Instrument Participants 2.500.000 SME-STREP 13

Abstract:Over 7000 allogeneic haematopoietic stem cell transplants (HSCT) are carried out each year in Europe alone, as a treatment for leukaemia and lymphoma. Techniques and cure rates are improving but the overall survival rate remains between 40-60%. This project will develop new proteomic, biological and genomic tests and tools for early diagnosis and monitoring of patient response to novel therapeutics for the most severe complication of HSCT; graft versus host disease (GvHD) and will bring to the clinic a new generation of diagnostics that will significantly improve HSCT therapy and patient outcome. The Consortium unites 5 European SMEs with expertise and markets in genomic and proteomic testing, diagnostic assay development and biochips, with clinical partners selected for their world leading research in HSCT and access to clinical samples and patient groups. The project will focus on the role of relevant genes and biomarkers associated with acute and chronic GvHD, using retrospective samples from established biobanks and prospective clinical trials to: 1) Identify novel bio and genomic markers for diagnostics; 2) Develop novel diagnostic tools using genomics, proteomics, in vitro bioassays and biochips; 3) Test the new diagnostics in animal models & on clinical samples; 4) Exploit the new tools for commercial use. The above will be realised by: 1) Development of diagnostic tests using single nucleotide polymorphism (SNP) analyses (SME IMGM), based on results from previous EC funded research (EUROBANK, TRANSEUROPE); 2) Using proteomics via mass spectrometry (evaluation/development of diagnostic patterns (SME MOSAIQUES), ELISA kits (SME APOTECH) and protein biochip prototypes (SME ORLA), for the development of fast high throughput technologies. 3) Development of novel reagents for monitoring graft versus leukaemia, GvHD and targeted therapy (SME MULTIMUNE; SME NASCACELL). 4) Comparative studies in an autoimmune disease model of inflammation; rheumatoid arthritis.

Web site:

not yet

Participants:Coordinator United Kingdom Austria Czech Republic France Germany Prof. Anne Dickinson, Haematological Sciences School of Clinical and Laboratory Sciences, The Medical School, University of Newcastle upon Tyne tel: +44 191 282 4259 fax: +44 191 222 5524 a.m.dickinson@ncl.ac.uk Hildegard Greinix, Universitaetsklinik fuer Innere Medizin 1, Medical University of Vienna, Vienna Ilona Hromadnikova, Cell Biology Laboratory, 2nd Medical Faculty, Charles University, Prague Gerard Socie, Service d'Hematologie Greffe de Moelle, Hospital Saint Louis, Paris Ernst Holler, Dept. Hematology/Oncology, University of Regensburg, Klinikum der Universitaet Regensburg, Regensburg Harald Mischak, Mosaiques Diagnostics GmbH, Hannover, SME Gabriele Multhoff, Department of Hematology and Oncology, University Hospital Regensburg, multimmune GmbH, Regensburg, SME Ralph Oehlmann, IMGM Laboratories GmbH, Martinsried, SME Hans-Jochem Kolb, Klinical Cooperation Group Hematopoietic Cell Transplantation, Institute of Molecular Immonology, Forschungszentrum fuer Umwelt und Gesundheit, GmbH, Muenchen Lars French, Dermatology, Geneva University Hospital & Louis Jeanet Skin Cancer Lab, University Medical Centre, University of Geneva Maximilien Murone, Apotech Corporation, Epalinges Amanda McMurray, Technology, Centre of Excellence for Nanotechnology, Micro & Photonic Systems, Newcastle upon Tyne Dale Athey, Nanotechnology Centre, Orla Protein Technologies Ltd, Newcastle upon Tyne, SME

Switzerland United Kingdom

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

IDENTIFICATION OF GENOMIC AND BIOLOGICAL MARKERS AS PREDICTIVE/DIAGNOSTIC/THERAPEUTIC TOOLS FOR USE IN ALLOGENEIC STEM CELL TRANSPLANTATION: TRANSLATIONAL RESEARCH TOWARDS INDIVIDUALISED PATIENT MEDICINEProposal acronym Contract n Duration (starting date) TRANS-NET MRTN-CT-2004-512253 4 years (01.01.2005) EC contribution () Instrument Participants 4.539.456 Marie-Curie RTN 12

Abstract:Allogeneic stem cell transplantation (HSCT) is a life saving therapy for haematological disorders (leukaemia and lymphoma, inherited immune disorders, and a plastic anaemia). Over 7000 such transplants are carried out each year in Europe. However the overall survival rate after HSCT is poor (40-60%), and cure of patients is hampered by clinical complications that arise post-transplant; largely due to genetic and biological differences which exist between a given patient and donor. These differences include transplantation antigens (major and minor histocompatibility antigens). Pioneering research by Partners, have indicated that a number of non-HLA gene polymorphisms also affect the severity and incidence of transplant related complications. There is an urgent need to improve patient-donor matching at both the biological and genomic level which would develop HSCT beyond the current state of the art. HSCT outcomes will be improved if predictive assays, diagnostic tools and new therapeutics were developed and ultimately used by HSCT clinicians for individual patient based medicine. TRANS-NET teams have expertise in predictive bioassays, genomics, diagnostics and novel therapeutics who will train researchers in the key technologies of, mRNA expression profiling, pathology, non-HLA immunogenetics and mechanisms of immune recognition; with the ultimate aim of applying the results of TRANS-NET in the HSCT clinical setting. TRANS-NET aims to: 1) Define new biological/genomic indicators and novel therapies for the potential development of new clinical strategies for improving the outcome and quality of life of HSCT patients; 2) Develop unique training programmes in genomics and immunobiology of transplantation and generate highly trained scientists with the ability to manage complex projects and understand the scientific challenges of individualised patient medicine; 3) Disseminate knowledge gained throughout the ERA and clinical HSCT centres across the EC.

Web site:

http://www.trans-net.org.uk

Participants:Coordinator United Kingdom Austria Czech Republic France Germany Prof. Anne Dickinson, Haematological Sciences, School of Clinical and Laboratory Sciences, University of Newcastle-Upon-Tyne tel: +44 191 282 4259 fax: +44 191 222 6794 a.m.dickinson@ncl.ac.uk Hildegard Greinix, Bone Marrow Transplantation Unit, Medical University of Vienna Ilona Hromadnkov, 2nd Medical Faculty, Charles University, Prague Nuala Mooney, INSERM U396, Immunogntique Humaine, Centre de Recherches Biomdicales des Cordeliers, Paris Ralf Dressel, Abt. Immungenetik, "Bereich Humanmedizin" Georg-August-University Goettingen Ernst Holler, Hamatology und Internistiche Onkologie, Klinikum der Universitt Regensburg & Gabriele Multhof, Department of Hematology and Oncology, University of Regensburg Hans Jochem Kolb, Klinikum Grohadern, Stammzelltransplantation, Ludwig Maximillian Universitt Medizinische Klinik III, Mnchen Markus Uhrberg, Institut fuer Transplantationsdiagnostik und Zelltherapeutika, Universittsklinikum Dsseldorf, Heinrich-Heine-Universitat, Dusseldorf Bent Rolstad, BM Transplantation Group, Dept. Anatomy, University of Oslo Lars French, Department of Dermatology, Geneva University Hospital, University of Geneva Mark Lawler, Cancer Molecular Diagnostics, CPL St James's Hospital, Dublin Walter Kolch, Institute of Biomedical and Life Sciences, University of Glasgow

Norway Switzerland United Kingdom

Commission: Directorate General for Research - Human ressources and Mobility Directorate - Marie Curie Actions

TRANSPLANTATION RESEARCH INTEGRATION ACROSS EUROPEProposal acronym Contract n Duration (starting date) TRIE LSSB-CT-2007-037540 1.5 year (01.03.07) EC contribution () Instrument Participants 450.000 SSA 5

Abstract:The overall objective of TRIE is to help realise ERA objectives by preparing the groundwork for an integrated, large-scale initiative in transplantation research in the European Union. This will be achieved through: 1. Identifying transplantation research topics which are best addressed by an integrated European action i.e. topics which cannot be adequately addressed at national level. 2. Confirming political and research funding agency support at national level for: Centralising existing programmes in these fields; Committing funds to new centralised programmes. 3. Identifying the common denominators on which a joint European initiative will be based and deciding on an optimal instrument for a future integrated initiative; 4. Preparing detailed implementation plans, both scientific and organisational so that these plans can be made operational following the mid-term review of FP7; 5. Presenting the final results and implementation plans at a high profile event at the European Parliament. Building such a novel integrated transplantation research programme across Europe depends on a careful and stepwise process involving key stakeholders, national research policy authorities, as well as the current ERA-NET project AllianceO. This cooperation will be assured through the establishment of two Advisory bodies: a Scientific Council made up of leading research scientists in the transplant field and a Stakeholders Forum made up of political representatives at European and national level, research agencies and funding bodies, academics, industry, patient organisations and other such groups. The TRIE proposal has already generated widespread European interest at both political and scientific level. Eleven leading scientists in transplantation research have pledged their commitment to the aims and activities of the Scientific Council and letters of support for this initiative have been received from public research agencies in nine EU countries.

Web site:

not yet

Participants:Coordinator Belgium Ireland Spain United Kingdom Prof. Michel Goldman, Institut d'Immunologie Mdicale, Universite Libre de Bruxelles, Charleroi (Gosselies), Bruxelles tel: +32 2 650 95 60 fax: +32 2 650 95 62 gefauche@ulb.ac.be Siobhan McQuaid, International Projects Department, ABU International Project Management Limited, Dublin, SME Blanca Miranda Serrano, National Transplant Coordination, Centro Nacional de Trasplantes y Medicina Regenerativa, Madrid Kathryn, WOOD, Nuffield Departement of Surgery, University of Oxford, The Chancellor, Masters and Scholars of the University of Oxford, Oxford Alejandro Madrigal, The Anthony Nolan Research Institute, The Anthony Nolan Trust, Hampstead, London

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

INTEGRATING Ethical, legal & societal aspects, training

A EUROPEAN MULTIMEDIA REPOSITORY OF SCIENCEProposal acronym Contract n Duration (starting date) EMRS LSHM-CT-2004-504755 4 years (01.08.04) EC contribution () Instrument Participants 675.000 SSA 5

Abstract:Life sciences hold promise to improve the quality of life in our society. Because of the complexity of the field, scientific, social and ethical uncertainties remain about many of the possible technological applications. Unresolved concerns may lead to rejection of beneficial technologies with negative impact on innovation and socio-economic fabric of our society. Constructive dialogue with the key stakeholders is needed to minimise unfounded concerns and maximise public empowerment on these complex issues, while at the same time, allowing a positive feedback to assure that science is moving forward in cohort with social needs and expectations. The European Multimedia Depository of Science (EMRS) will make a strong effort to bring the scientific world closer to three chosen key stakeholders: the general public, educators and media. EMRS will address European co-ordinated LifeSciHealth scientific activities in the area of advanced genomics, its application for health and combating of major diseases. This will be done through a number of approaches and deliverables. The chosen stakeholders will be reached by using effective communication platforms that offer high impact value: video, multimedia, television, internet and publishers.The main deliverables of the project are sixteen high quality short films. There will be three levels of disseminating the film contents: i) through broadcasting media, namely Discovery Channel and European Broadcasting Union; ii) using an on-line internet based multimedia library and iii) by direct distribution of VHS, CD- ROM and DVD to target groups through our four associated networks and members of our extensive advisory board. In support of these activities two additional actions will be undertaken: creation of internet based Rapid Response Science Network (RRSN) where scientists will answer questions related to the topics addressed in the project and three focus meetings with proceedings to be published by Springer. The first lot of 4-5 minute films are based on a number of current EU integrated projects, covering cell differentiation (primarily stem cells). Film 1 deals with new advances in stem cell research - therapeutic angiogenesis - where bone marrow epithelial progenitor cells are injected into the heart tissue of heart attack patients to encourage vessel regeneration. Film 2 addresses the science behind vessel regeneration, looking especially at zebra fish. Film 3 deals with the theory of cell differentiation, the so called epigenetic code. The second lot will concern twin studies, and life style issues (exercice, nutrition and diabetes). The third lot will be programmed according to the feedback to the first ones.

Web site:

http://www.eusem.com

Participants:Coordinator France Austria Germany Ireland Netherlands Dr. Paul Pechan, Ludwig Maximilians University, Munich tel: +49 816 171 342 1 fax: +49 816 171 451 1 ppechan@compuserve.com Barbara Streicher, Dialoggentechnik, Vienna Heidi Bohle, Visions Unlimited Medien GmbH, Otterfing Catherine Adley, Biotechnology Awareness Centre, University of Limerick Gerhard Ernst de Vries, ProBio Partners VOF, Overschild

Commission: Directorate General for Research - Health Directorate - Unit F1 Strategy and Policy

EUROPEAN HUMAN EMBRYONIC STEM CELL REGISTRYProposal acronym Contract n Duration (starting date) EU hESC registry LSSM-CT-2006-037820 3 years (01.03.07) EC contribution () Instrument Participants 1.000.000 SSA 13

Abstract:Human embryonic stem cell (hESC) research holds promise for the development of therapies for degenerative pathologies, offers a tool for drug discovery and toxicity tests, for studying human development, disease physiology and gene control. hESC lines are currently derived in an increasing number of laboratories in Europe and around the world. A detailed registry of available cell lines will promote the validation and efficient use of these precious cells for research and application. Comparable information is needed about the origin of the cell lines, the methodology and standards for their derivation and the characteristics to assess their availability for research and future therapies. The growing use of hESC by the scientific community demands a high quality and comprehensive registry. The aim of the proposed European hESC registry is to promote access to all hESC lines derived in Europe and transparency about their characteristics. Only well defined and adequately characterised hESC lines according to the parameters established by the registry be listed. To determine listing decisions, the features of the cell lines will be evaluated according to defined scientific and quality standards. Data such as the origin, the derivation methodology, as well as the different parameters used for characterisation will be recorded for each hESC line in the registry. Contact data and legal status will also be available for each cell line. Each cell line will be annotated with essential and useful information on their characteristics and applications. Registry of the database and website will facilitate the continuous mapping of the research and legislative landscapes in a topographical online design. The registry will also serve as a communication and consultation platform for hESC researchers, clinical groups, patients groups and the public at large for information on hESC.

Web site:

http://www.cellnet.org/

(menu: networks > hESC-Registry)

Participants:Coordinator Germany Belgium Czech Republic Finland France Germany Israel Netherlands Spain Sweden Turkey United Kingdom Dr. Joeri Borstlap, Dep. of Experimental Surgery, Charit, Universittsmedizin Berlin tel: +49 30 450 552 501 fax: +49 30 450 576 907 joeri.borstlap@charite.de Karen Sermon, Research Group Reproduction and Genetics, Vrije Universiteit Brussel Petr Dvorak, Department of Molecular Embryology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague Timo Tuuri, Biomedicum Helsinki Carine Camby, Agence de la Biomedecine, St Denis La Plaine Andreas Kurtz, Licensing office for human embryonic stem cell research and head, stem cell lab, Robert Koch-Institut, Berlin Benjamin Reubinoff, The Hadassah Human Embryonic Research Center, Hadassah University Hospital, Jerusalem Christine Mummery, Hubrecht Laboratory, Utrecht Anna Veiga, Stem Cell Bank, Centre de Medicina Regenerativa / Institut Dexeus, Barcelona Agustn G. Zapata, Instituto de Salud Carlos III, Madrid Outi Hovatta, Department of Clinical Science, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm Necati Findikli, ART & Reproductive Genetics Centre, R&D Laboratory, Istanbul Memorial Hospital, Sisli/Istanbul Glyn Stacey, U.K. Stem Cell Bank, National Board for Biological Standards, South Mimms

Commission: Directorate General for Research - Health Directorate - Unit F1 Strategy and Policy

EUROPE, ITS CITIZENS AND STEM CELL RESEARCH: A ONE-DAY CONFERENCE

Proposal acronym Contract n Duration (starting date)

EUROCITS LSSM-CT-2005-018699 16 Months (01.07.05)

EC contribution () Instrument Participants

500.000 SSA 1

Abstract:To organise a one-day conference of estimated 500 participants providing the latest scientific information on the research on and use of Stem Cells in severe disorders. The goal of this conference is to promote a real dialogue on stem cell research between science and society. The understanding of most of the European population on the topic of stem cell research and its potential is limited. They need help to focus on research priorities, ethical questions and to contribute to an informed debate. Patients, as citizens of Europe, will be able to debate with other stakeholders some of the basic ethical challenges underpinning this research and its application. The conference will use lay language and there will be ample opportunity to pose questions to experts in this very sensitive field of research. Similar conferences have been organised in the past by scientists for scientists but this event will be planned with particular focus on the impact of research on patients. EFNA, the European Federation of Neurological Associations, an umbrella organisation for panEuropean patient federations in the field of brain disorders, will be the organiser. Patients from a wide range of disorders, carers, health professionals, scientists, ethicists, politicians, media, employers and health insurers will be invited to take part. The event will be held in Brussels with free registration. The working language will be English, with simultaneous translation into makor EU languages. The newly-integrated EU countries will have active participation by specially enabling them to take part in the event. To maximise the results, the conference proceedings will be disseminated through radio and TV transmissions, websites, and publications in popular and scientific journals, newsletters and on CD-rom. It is intended that this conference will lead to clearer understanding of the issues surrounding stem cell research and an integrated way forward in Europe to benefit the European citiziens.

Web site:

http://www.erastepps2005.eu.com

Participant:Coordinator Belgium Mrs Mary G. Baker, European Federation of Neurological Associations (EFNA), Brussels tel: +39 0554 362 098 fax: +39 0554 271 280 efna@pharm.unifi.it

Commission: Directorate General for Research - Health Directorate - Unit F1 Strategy and Policy

CHIMERAS AND HYBRIDS IN COMPARATIVE EUROPEAN AND INTERNATIONAL RESEARCH SCIENTIFIC, ETHICAL, PHILOSOPHICAL AND LEGAL ASPECTSProposal acronym Contract n Duration (starting date) imgbchimerashybrids SAS6-CT-2005-016708 2 years (01.10.05) EC contribution () Instrument Participants 600.424 CA 23

Abstract:The objective of the proposed project is to develop a deeper and comprehensive understanding of the fundamental problems in the research on Chimeras and Hybrids by means of a European and International aligned exchange and a partnership of co-operation, dialogue and network with Scientists from the ranges of the natural sciences, ethics, philosophy and jurisprudence, as well as with External Agents from Society under the co-ordination of the IMGB. The new and partly still unconsidered problem complex of mixing creatures and blending techniques of human being and animals is at the centre of attention in natural scientific, ethical, philosophical and legal analysis. The interdisciplinary and international analysis and examination of human being - animal Chimera and Hybrid formations includes therefore fundamental and basic problem complexes in each research discipline, such as the creation possibilities and different kinds of characteristics of Chimeras and Hybrids, the production of hybrid ES-cells, the creation and the use of transgenic animals, the open questions of potential therapies, the ethical and moral evaluation, as well as the constitutional and legal aspects of human dignity, freedom of research and protection of animals. The realisation of the objective will be achieved by compiling concepts, proposals for research practices, recommendations and decision supports for decision makers, thus enabling a structural and enduring interrelation between rapid progress in scientific research and basic legal, ethical and philosophical principles. By means of reports and different elements of dynamic interaction, through speeches and discussions on basic and specific problems in the framework of Conferences and Workshops for compiling a final synthesis report, the proposal will bring Science and Society closer together and will also stimulate the development of emerging questions on Chimeras and Hybrids in the European Research Area.

Web site:

http://www.chimbrids.org

Participants:Coordinator Germany Austria Belgium Canada China Czech Republic France Germany Hungary Israel Japan Netherland Spain Sweden Switzerland United Kingdom United States Prof. Dr. Jochen Taupitz, Universitt Mannheim, Institute for Medical Law (IMGB), Mannheim tel: +49 621 181 1934/1990 fax: +49 621 181 3555 taupitz@jura.uni-mannheim.de Erwin Bernat, Universitt Graz, Institute for Civil Law, Foreign and International Private Law, Graz Walter Lesch, Universit Catholique de Louvain, Faculty of Theology and Canon Law, LLN Bartha-Maria Knoppers, Universit de Montral, Centre de Recherche en Droit Public, Montral Derek van der Kooy, University Toronto, Department of Medical Genetics & Microbiology, Toronto Kuisheng Dai, University of Nanjing, German Institute for Business Law, Nanjing Qi Zhou, Chinese Academy of Science, Institutee of Zoology, Beijing Filip Krepelka, Masarykova unverzita v Brno, Brno Josef Kure, Masarykova unverzita v Brno, Brno Sonia Desmoulin, Univ. Paris I, Centre Recherche Droit des Sciences et des Techniques, Paris Jean-Paul Renard, INRA, Dpart. Physiologie animale & systmes d'levage, Jouy-en-Josas Michael Bader, Max-Delbrck-Centrum Berlin, Institute or Department, Town Jan C. Joerden, Europa-Universitt-Viadrina Frankfurt, interdisciplin. Center for Ethics, Frankfurt Eckhard Wolf, Ludwig-Maximilians-Universitt Mnchen, Veterinary School, Mnchen Andras Dinnyes, Agricultural Biotechnology Center, Institute or Department, Town

Amos Shapira, Tel Aviv University, Law Faculty, Tel Aviv Motomu Shimoda, Osaka University, Osaka School of International Public Policy, Osaka Fumio Tokotani, Osaka University, Osaka School of International Public Policy, Osaka Marcus Duewell, Universiteit Utrecht, Institute for Ethics, Utrecht Carlos Maria Romeo-Casabona, Universidad de Deusto, Chair BBVA Foundation Provincial Government of Biscay in Law and the Human Genome, Bilobao/Donostia Elisabether Rynning, Uppsala Universitet, Faculty of Law, Uppsala Rainer Schweizer, Universitt St.Gallen, Law School, St Gallen Deryck Beyleveld, University Sheffield, Sheffield Institute for Biotechnological Law and Ethics, Sheffield Autumn Fiester, University Pennsylvania, Institute or Department, Town Timothy Jost, Washington and Lee University, Law School, Lexington, VA

Commission: Directorate General for Research - Science & Society Directorate - Unit C3 Ethics

EUROPEAN LABCOURSE: ADVANCED METHODS FOR INDUSTRIAL PRODUCTION, PURIFICATION AND CHARACTERISATION OF GENE VECTORSProposal acronym Contract n Duration (starting date) INDUSTRYVECTORTRAIN LSHB-CT-2003-505516 21 months (01.01.2004) EC contribution () Instrument Participants 176.000 SSA 2

Abstract:To allow gene & cell therapies to evolve more quickly into biomedical sciences, it is necessary to disseminate throughout the scientific community: (i) the basic knowledge of the biology of vectors and stem cells, (ii) the expertise of their production, purification and characterisation, (iii) the assessment of their therapeutic efficiency and bio-safety (iv) the definition of the regulatory frames in which these tools can be transformed into new medicines and commercially exploited. The state of this evolution is today still far from its objective, since the insufficient knowledge of the biology of vectors and stem cells, a scarce co-ordination of research projects and the absence of integration of the activities of the actors operating in different concerned areas (research, industry, health products regulation and marketing). Therefore, the realisation of a multidisciplinary training programme, which integrates various scientific and technological approaches, is necessary today to address a real need of the scientific community. The activity scheduled in this proposal concerns a 2-weeks theoretical and practical course, where 32 young researchers (selected on the basis of scientific excellence) will be trained on the advanced processes of vector production, purification and quality control for gene therapy clinical trials. The course is expected to gather young scientists from industrial and academic institutions, coming from several EU and candidate countries. It will present training and scientific innovations: for the first time the various aspects of the development of vector technology from the bench to the industrial level will be provided to the community. Theoretical modules will be open to large public, namely, biotech firms and regulatory agencies, where the status of the art will be presented and discussed. The course will (a) allow young researchers from industries and academia to acquire a multidisciplinary training on vectors development, the definition of new ethical and legal frames, and socio-economical implications; (b) implement an environment in which all concerned institutions (public and private) and regulatory agencies will exchange respective expertise to develop process towards the economical exploitation of new therapeutic tools and processes.

Web site:

http://www.vecteurotrain.org

Participants:Coordinator France France Dr. Mauro Mezzina, GENETHON, Evry tel: +33 1 6947 1023 fax: +33 1 6077 8698 mezzina@genethon.fr Gilles Waksman, Universite de Evry-Val d'Essonne, Evry

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

EUROPEAN LABCOURSE : TOWARDS CLINICAL GENE THERAPY : PRECLINICAL GENE TRANSFER ASSESSMENTProposal acronym Contract n Duration (starting date) INVIVOVECTORTRAIN LSHB-CT-2003-503219 21 months (01.07.03) EC contribution () Instrument Participants 161.620 SSA 2

Abstract:To allow gene & cell therapies to evolve more quickly into biomedical sciences, it is necessary to disseminate throughout the scientific community: (i) the basic knowledge of the biology of vectors and stem cells, (ii) the expertise of their production, purification and characterisation, (iii) the assessment of their therapeutic efficiency and bio-safety with an adequate animal experimentation, (iv) the definition of the regulatory frames in which these tools can be transformed into new medicines and commercially exploited. The state of this evolution is today still far from its objective, since the insufficient knowledge of the biology of vectors and stem cells, a scarce co-ordination of research projects and the absence of integration of the activities of the actors operating in different concerned areas (research, industry, health products regulation and marketing). Therefore, the realisation of a multidisciplinary training programme, which integrates various scientific and technological approaches, is necessary today to address a real need of the scientific community. The activity scheduled in this proposal concerns a 2weeks theoretical and practical course, where 32 young researchers (selected on the basis of scientific excellence) will be trained on the basic procedures of gene transfer into animals, targeting major organs (liver, brain, muscle, lung), and of imaging-monitored gene expression in alive animals. The course is expected to gather young scientists of academic and industrial institutions, coming from several EU and candidate countries. It will present training and scientific innovations: for the first time the vector production technology will be combined with the in vivo evaluation. Theoretical modules will be open to large public, namely, biotech firms and regulatory agencies, where the status of the art will be presented and discussed. The course will (a) allow young researchers from academia and industries to acquire a multidisciplinary training on vectors development from bench levels to medicines, including the industrial development and the definition of new ethical and legal frames; (b) implement an environment in which all concerned institutions (public and private) and regulatory agencies will exchange respective expertise to develop process towards the economical exploitation of new therapeutic tools and processes.

Web site:

http://www.vecteurotrain.org

Participants:Coordinator France Spain Dr. Mauro Mezzina, GENETHON, Evry tel: +33 1 6947 1023 fax: +33 1 6077 8698 mezzina@genethon.fr Miguel Chillon Rodriguez, Universitat Autonoma de Barcelona (UAB)

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

REPROGENETICS: THE ETHICS OF MEN MAKING MENProposal acronym Contract n Duration (starting date) REPROGENETICS (CLEMIT) SAS6-CT-2003-003286 3 years (01.04.04) EC contribution () Instrument Participants 980.000 STREP 6

Abstract:During the last 5 years genetics and reproductive medicine have merged to form Reprogenetics and come to represent revolutionary possibilities for studying grave diseases and developing new therapies. Specific scenarios are developed that may result in the technical possibility to change the genetic constitution of humans and their descendants. In fact, in a limited way, some technologies may already do this. The overwhelming possibilities presented by such developments have been met with concern and reignited the debate on the question if men might be able to design and change the genetic structure of other men and if men may be able to create new human beings. The values at stake in these issues are often felt as deeply human and there is a widespread conviction that several of the new technical possibilities should be banned or at least placed under moratorium no matter how promising they may be. The situation of a moratorium or ban might create a false impression of ethical clarity and yet, the content and strength of ethical arguments applied has not yet been analysed or made explicit. When not accompanied by a consistent study of conditions under which it may be lifted, a moratorium would no longer be a sign of ethical strength but of indecisiveness and a lack of ethical decision-making. Still in circles of private and academic research not guided by ethical and social reflection, but as an arbitrary result of unknown market forces and the private ambition of researchers and research institutes. The project will make a comparative analysis of the ethical aspects of hot issues in gene therapy and cloning, study the ambiguities and inconsistencies of current law and theory, try to strengthen them and, when needed, distinguish contexts that share names, but may have completely different ethical implications.

Web site:

http://www.clemit.net

Participants:Coordinator Belgium France Italy Norway Spain United Kingdom Prof. Guido Van Steendam, International Forum for Biophilosophy, Leuven tel: +32 16 23 11 74 fax: +32 16 29 07 48 Guido.VanSteendam@cs.kuleuven.ac.be Jacques Mallet, Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs, Centre National de la Recherche Scientifique, Paris Cinzia Caporale, Einaudi, Universita degli Studi di Roma La Sapeinza, Rome Matthias Kaiser, National Committees for research Ethics, NENT, Oslo J. Carlos Romeo Casabona, Catedra Interuniversitaria Fundacion BBVA - Diputacion Foral de Bizkaia, de Derecho y Genoma Humano, Universidad del Pais Vasco (UPV/EHU), Bilbao John Harris, Institute of Medicine Law and Bioethics (IMLAB), The Victoria University of Manchester

Commission: Directorate General for Research - Science & Society Directorate - Unit C3 Ethics and Science

FROM CELLULAR SENESCENCE AND CELL DEATH TO CANCER AND AGEINGProposal acronym Contract n Duration (starting date) SENECA LSHM-CT-2006-037312 2 years (01.10.06) EC contribution () Instrument Participants 142.800 SSA 3

Abstract:Age is the most important demographic risk factor for many life-threatening human cancers. About two-thirds of all diagnosed cancers occur in people over the age of 65. Since tumours include cancer cells with an extensive proliferative history, subject to senescence and senescence-avoidance mechanisms, cancer researchers commonly study various aspects of biological ageing. However, many cancer specialists, clinicians, and industry representatives remain unaware of what ageing research can offer for cancer prevention and therapy. Presently the research fields of biological ageing and cancer in Europe remain largely fragmented, without structured links or widespread interdisciplinary approaches. Therefore, the main goal of the planned 2_-day, 300-participant conference is to improve the awareness of ageing research among cancer researchers and stimulate cooperation aimed at redefining molecular targets and improving cancer prevention and therapeutics in the ageing population. The conference will provide a forum for scientific exchange among outstanding European scientists working in the fields of ageing and cancer. The discussion will focus around such issues as: DNA damage, telomeres and telomerase in cancer and ageing, effects of tissue environment in tumour formation, impact of the ageing immune system on cancer immunosurveillance and immunotherapy, links between stem cells and cancer and ageing, links between tumour suppression and cellular senescence, and cellular senescence as a new target in anticancer therapy. The conference will also bring together other key stakeholder groups such as policy makers, clinicians and industry. The proposed event will contribute to attracting scientists from cancer research and other disciplines to ageing research. It will help establish sustainable organizational links between these two closely related scientific fields, structuring European research in oncogerontology.

Web site:

http://www.seneca2007.eu

Participants:Coordinator Poland Germany Russia Prof. Ewa Sikora, Department of Cellular Biochemistry, Laboratory of Molecular Bases of Aging, Instytut Biologii Doswiadczalnej im. M. Nenckiego Polskiej Akademii Nauk, Warsaw tel: +48 22 589 2436 fax: +48 22 589 2489 e.sikora@nencki.gov.pl Graham Pawelec, Innere Medizin II, Zentrum fr Medizinische Forschung, Tbingen Ageing and Tumour Immunology Group, Eberhard-Karls-Universitt Tbingen, Tbingen Vladimir N. Anisimov, Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, St.Petersburg

Commission: Directorate General for Research - Health Directorate - Unit F5 Biotechnology and Applied Genomics

STEM CELL PATENTS: EUROPEAN PATENT LAW AND ETHICSProposal acronym Contract n Duration (starting date) StemCellPatents LSSB-CT-2004-005251 4 Years (01.01.05) EC contribution () Instrument Participants 249.257 SSA 5

Abstract:Stem cell research, and embryonic stem cell research in particular, offers the prospect of developing new therapies for serious or life-threatening diseases. But for the potential offered by stem cell research to be realized into therapeutic products, industrial or commercial investment is required. At the same time, embryonic stem cell research raises difficult and controverted moral questions which are reflected in the variety of moral perspectives and regulatory regulatory regimes already adopted or currently being developed in EU member States which vary from total prohibition to qualified authorization in varying forms and degrees. The diversity of legal regimes regulating embryonic stem cell research in Europe together with the subsidiarity principle which devolves competency on legislation concerning ethical questions to members States, has created uncertainty as to the legal scope of the "moral exclusion" clause in Article 6 of Directive 98/44EC of 6 July 1998 on the legal protection of biotechnological inventions. Clarification on the scope of the Directive is essential to foster research and investment in Europe whilst ensruring that such research is conducted within clear ethical limits which address the concerns of society. The project aims to provide an analysis of the EU patent system, as applied to biotechnological inventions in general and to embryonic stem cell related technology in particular with a view to ascertain the legal effect of ethical or legal divergence on European patent law. The multi-faceted nature of the question raised requires the combined efforts of experts from different disiplines to contribute to the coordination, analysis and dissemination of knowledge in this area. The multidisciplinary character of the Consortium is intended to bring the required breadth and depth of expertise to bear on the project.

Web site:

http://www.nottingham.ac.uk/law/StemCellProject

Participants:Coordinator United Kingdom Belgium Canada Sweden United Kingdom Dr. Aurora Plomer, The University of Nottingham, School of Law, Nottingham tel: +44 115 9515717 fax: +44 115 9515696 Aurora.Plomer@nottingham.ac.uk Francis Crawley, European Forum for Good Clinical Practice, Brussels Bartha Knoppers, Universite de Montreal, Faculty of Law, Montreal (Quebec) Marianne Levin, Stockholm University, Institute for Intellectual Property and Market Law (IFIM), Stockholm John Sinden, ReNeuron Ltd, Head Officer, Guildford, SME

Commission: Directorate General for Research - Health Directorate - Unit F1 Strategy and Policy

A WORLDWIDE STUDY OF UMBILICAL CORD CELL BANKINGProposal acronym Contract n Duration (starting date) SAS5-CT-2002-30038 5 months (01.10.02) EC contribution () Instrument Participants 13.000 1

Abstract:Since a few years a different organisations are active in the banking of umbilical cord cells. Umbilical cord blood contains stem cells which are similar to the cells found in human bone marrow. These cells are now stored for 2 main reasons: either for the benefit of other patients who could benefit from a stem cell transplant or for the individual donor at a later stage in his or her life (autologous transplantation). The objective of the study is to understand the extent of these practices, the way they are organised and their economic impact.

Web site:

http://www.ccels.cf.ac.uk/pubs/gunningpaper.html

Participants:Contractor United Kingdom Dr. Jennifer Gunning, Consultant in Bioethisc and Science Affairs tel: +44 1225 316629 fax: +44 1225 316629 gunning@cf.ac.uk

Commission: Directorate General for Research - Science & Society Directorate - Unit C3 Ethics and Science

ANNEX Classification of projects by tissues, organs and diseases

OBJECTIVES AND METHODOLOGYA given project can appear under several sub-domains, either in organ/tissues, or diseases. For instance, the project MCSCs (Migrating cancer stem cells in breast and colon cancer) will appear in "Ectoderm-derived epithelia", "endodermderived organs", and "cancer". Projects not related to any of these domains were classified under "transversal issues". In the pdf version of the book, this cross-cutting classification is a second way of accessing the projects using the bookmarks, where clickable links give access to the projects listed under this second table of content.

ORGANS & TISSUESNeurectoderm-derived tissues and organs: brain, spine, nerves, sensory organsARTEMIS, EuroHear, EUROSTEMCELL, EVI-GENORET, INTERDEVO, NanoEar, NEURONE, NEUROscreen, NSR, Plurigenes, RESCUE, STEM-HD, STEMS, STEMSTROKE, STROKEMAP, X-ALD.

Ectoderm-derived epithelia: skin and annexes, cornea, ectoderm-related exocrine glands

CORNEA ENGINEERING, EPISTEM, EuroCSC, EUROSTEMCELL, MCSCs, SKINTHERAPY, STEPS, THERAPEUSKIN, Ulcer Therapy

Endoderm-derived organs: digestive, respiratory and urogenital tracts, glands and annexes

BARP+, BETACELLTHERAPY, CELLS INTO ORGANS, EPI-VECTOR, EUGENE2, EuReGene, EURO-Laminopathies, EuroSTEC, KIDSTEM, LIVEBIOMAT, REGULATORY GENOMICS

Mesoderm-derived tissues and organs: connective tissues, muscles, tendons, fascia, bones, cartilage, fat

AUTOBONE, CELLS INTO ORGANS, EPI-VECTOR, EURO-Laminopathies, EuroBoNet, EuroSTEC, EUROSTEMCELL, EXPERTISSUES, GENOSTEM, HIPPOCRATES, MYOAMP, MYOCARDIAL REPAIR, MYORES, NANOBIOCOM, NEWBONE, OsteoCord, SILKBONE, SmartCaP, STEPS, SyntheGeneDelivery

Organs and tissues of mesodermal and composite origin: heart, blood vessels, lymphatic vessels

BIOSYS, CELLS INTO ORGANS, EURO-Laminopathies, EVGN, HeartRepair, INVITROHEART, LYMPHANGIOGENOMICS, MCSCs, MYOCARDIAL REPAIR, SC&CR, VASCUPLUG

Other organs and tissues of composite origin: blood, hematopoeitic organs, immune system organs

BARP+, BETACELLTHERAPY, CELLS INTO ORGANS, EPI-VECTOR, EUGENE2, EuReGene, EURO-Laminopathies, EuroSTEC, KIDSTEM, LIVEBIOMAT, REGULATORY GENOMICS

DISEASESCancersALLOSTEM, Anti-tumor targeting, CONTROL CANCER STEM, E.E.T.-Pipeline, EuroBoNet, EuroCSC, EUROPEAN LEUKEMIANET, EUROPEAN MCL NETWORK, EUROXY, FIRST, GIANT, M3CS-TU TH, MCSCs, MOL CANCER MED, MSCNET, ONCASYM, REGULATORY GENOMICS, SENECA, TUMOR-HOST GENOMICS

Rare diseases (and some less rare heritable diseases)

CONSERT, EPISTEM, EURO-Laminopathies, SKINTHERAPY, STEM-HD, SyntheGeneDelivery, THERAPEUSKIN, X-ALD

TRANSVERSAL ISSUES3G-SCAFF, CARCINOGENOMICS, CellPROM, CLINT, CRYSTAL, Custom-IMD, DNA REPAIR, EMBRYOMICS, EMRS, ESTOOLS, EU hESC registry, EUCOMM, EUROCITS, EuTRACC, FunGenES, imgbchimerashybrids, INDUSTRYVECTORTRAIN, INTHER, INVIVOVECTORTRAIN, MODEST, NEURO, PREDICTOMICS, REPROGENETICS, ReProTect, SIROCCO, StemCellPatents, THE EPIGENOME, TherCord, TRANSCODE, VITROCELLOMICS

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