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  • CNG - PROGRAMMES
    Timothy J Professor Tel 44 02083834253 Fax 44 02083838577 Email Contact Organisation MEDICAL RESEARCH COUNCIL MRC CLINICAL SCIENCES CENTRE CSC 20 Park Cresent LONDON UNITED KINGDOM Project description Determining the molecular basis of natural phenotypic variation including inter individual susceptibility to common diseases is a central challenge of post genome genetics The rat is a leading model species for research in physiology pharmacology and toxicology and for the study of a wide range of common genetically complex human diseases Decades of exquisite phenotyping and detailed analyses in rat experimental crosses have led to localization of hundreds of quantitative trait loci QTLs containing genes that confer susceptibility to complex disease phenotypes However in common with studies in other organisms few genes underlying these genetically complex traits have as yet been identified The availability of the rat genome sequence and genome scale technologies along with the ability to clone fertile adult rats has substantially advanced the potential for functional genomics research in the rat model The European Rat Tools for Functional Genomics EURATools consortium draws together leading European researchers in rat genetics pharmacology toxicology disease pathophysiology and genome biology and informatics The central aim of this project is the development of integrated genome tools that will generate knowledge which can be translated into improvements in healthcare for highly prevalent diseases in the European Union The EURATools aims will be achieved by integrating high throughput sequencing and genotyping with informatics by intensive analysis of phenotypes gene sequence and gene expression in congenic strains to identify genes and regulatory pathways for a wide range of rat disease phenotypes and by establishment of optimised protocols for rat gene targeting These new resources will significantly improve our understanding of complex genetic traits and will enhance prospects for drug development and strategies for preventing and treating some

    Original URL path: http://www.cng.fr/en/projects/fp6_euratools.html (2016-01-29)
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  • CNG - PROGRAMMES
    about the development and function of the inner ear 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 The identification of genes underlying sensorineural HI in humans and mice 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 The standardisation implementation and development of technologies The 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 Participants PHILIPPS UNIVERSITET MARBURG GERMANY UNIVERSITÄTSMEDIZIN GÖTTINGEN GEORG AUGUST UNIVERSITÄT GÖTTINGEN STIFTUNG ÖFFENTLICHEN RECHTS GERMANY INSERM TRANSFERT SA FRANCE MAX DELBRÜCK CENTRUM FÜR MOLEKULARE MEDIZIN

    Original URL path: http://www.cng.fr/en/projects/fp6_eurohear.html (2016-01-29)
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  • CNG - PROGRAMMES
    THE UNIVERSITY OF OXFORD WELLCOME TRUST CENTRE FOR HUMAN GENETICS University Offices Wellington Square OXFORD UNITED KINGDOM Project description The theme of this proposal is to develop methodologies that integrate functional genomic tools and genetic strategies to address major unresolved questions concerning the molecular basis of common diseases using coronary artery disease CAD as an example Progress in functional genomics technologies have dramatically increased the density of gene expression datasets providing information on the expression of individual genes and gene networks at the levels of transcription translation protein abundance and activity and metabolic processes They will impact prevalent human complex disorders by providing new information for disease prevention and treatment Risk factors of CAD represent dominant causes of premature death and disability Owing to the complexity of CAD our understanding of the pathophysiological processes involved is limited In this programme implemented by international investigators and SMEs we shall use functional genomics technologies metabonomics proteomics and transcriptomics to generate a comprehensive and multidimensional description of well defined states of CAD in selected clinical cohorts and animal models which will be used as a platform for studying the causes of CAD We will initially test the power of high density functional genomic

    Original URL path: http://www.cng.fr/en/projects/fp6_fgentcard.html (2016-01-29)
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  • CNG - PROGRAMMES
    and immunology into the causes of asthma in the European Community Exceptional epidemiological and clinical surveys have already been assembled of childhood and adult asthma with inclusive information on environmental factors such as tobacco smoke air pollution nutrition allergen exposure and industrial agents DNA and serum have been stored for analyses This resource of 40 000 subjects will be extended to include severe asthmatics for genomic and proteomic analyses GABRIEL will comprehensively screen candidate genes and perform whole genome association studies to identify all important genetic influences on asthma with unmatched power to verify positive findings The large body of results from the study will be exploited by statistical and bioinformatics groups experienced in handling data of this complexity GABRIEL will identify all important gene environment interactions underlying asthma in the European Community and the results will be translated in cellular and genomic models to identify their molecular mechanisms Microbial exposures in rural farming environments result in a dramatic reduction in the development of asthma indicating that effective tools for the prevention of asthma can be developed The consortium will therefore systematically study rural farming environments Cellular and genomic models to identify the molecular mechanisms of protective environments will be developed as screens for novel therapeutics and the commercialisation of consortium results GABRIEL contains a strong and innovative ethical component which together with involvement of the JRC will ensure integration of the results into the European knowledge base for patient understanding and disease prevention Participants BCF DIAGNOSTICS LTD IRELAND COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES FRANCE CORPORACION DE PROMOCION UNIVERSITARIA UNIVERSIDAD SAN FRANCISCO DE QUITO ECUADOR INSTITUTE OF MEDICAL GENETICS TOMSK SCIENTIFIC CENTER OF THE SIBERIAN BRANCH OF RUSSIAN ACADEMY OF MEDICAL SCIENCES RUSSIAN FEDERATION INSTITUTE OF BIOCHEMISTRY AND GENETICS OF UFA SCIENCE CENTRE OF RAS RUSSIAN

    Original URL path: http://www.cng.fr/en/projects/fp6_gabriel.html (2016-01-29)
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  • CNG - PROGRAMMES
    LABORATORY OF CANCER GENETICS LABORATORY OF MOLECULAR AND CELL BIOLOGY Via dei Monti di Creta 104 ITALY Project description Genetic skin diseases comprise almost 300 rare but often severe and even life threatening diseases and syndromes Despite recent identification of causative genes in a number of these disorders the molecular bases of several others are still unknown and often the function of the identified disease gene products remains an unsolved mystery In addition disease number and rarity impair proper management and no curative therapy is available By bringing together clinicians researchers and patient associa tions GENESKIN aims to generate accessible knowledge and improve health care service structures for affected people The focus is on five major disease categories epithelial adhesion disorders keratinization disorders ectodermal dysplasias connective tissue diseases DNA repair disorders For each group a clinical and laboratory network will generate and disseminate a list of reference centers with services offered diagnostic questionnaires protocols gene cards mutation database diagnost ic reagent lists and ongoing clinical trial list The research topics to be co ordinated in GENESKIN deal with improved early post natal and pre natal diagnosis by novel immunohistochemical biochemical and molecular tests identification of new genes involved in genetic skin diseases by collecting a sizable number of biological samples definition of genotype phenotype correlation and characterisation of newly identified gene product functions by creation of a sample Databank Knowledge dis semination and improved management will also be insured through the organisation of involved personnel training Finally pan European communication among patients organisations ethic committees physicians and scientist will be promoted The informati on regarding clinical diagnostic protocols lists diagnostic and research tools and communication among different groups will be integrated and disseminated through a dedicated web site Participants INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE FRANCE

    Original URL path: http://www.cng.fr/en/projects/fp6_geneskin.html (2016-01-29)
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  • CNG - PROGRAMMES
    Contact Organisation KING S COLLEGE LONDON SGDP CENTRE Strand LONDON UNITED KINGDOM Project description A fundamental function of the brain is to evaluate motivational and emotional significance of stimuli and to adapt behaviour accordingly We hypothesize that genetically influenced individual differences in brain responses to reward punishment and emotional cues in adolescents mediate risk for mental disorders with a major public health impact Neuroimaging permits the measurement of specific brain functions implicated in the etiology of mental disorders and link them to genetic variations and behavioural characteristics relevant to disease processes The goal of the present study is to identify the neurobiological and genetic bases of these traits and to assess their relevance for mental disorder To this end we will perform the first multicentre functional and structural genetic neuroimaging study of a cohort of 2000 14 year old adolescents Intermediate phenotypes of risk for adolescent mental illness will be explored based on cognitive behavioural clinical and neuroimaging data To determine the predictive value of intermediate phenotypes and genetics for development of mental disorders our cohort will be psychometrically assessed during recruitment and longitudinally at year 4 age 16 18 of this proposal DNA samples and phenotype database for the cohort will create a powerful resource for present and future genetic investigations In the present study we will assess association with markers of genes chosen from existing genomic information and from our studies of animals selected for extreme phenotypes of impulsivity and other relevant behavioural traits Results obtained will be validated in 1000 siblings from the Canadian Saguenay youth neuroimaging study The IMAGEN study will help elucidate the neural basis of mental disorders and will lay the groundwork for development of treatments that target specific pathological processes across mental disorders rather than heterogeneous categories of mental illness Participants TECHNISCHE UNIVERSTITÄT

    Original URL path: http://www.cng.fr/en/projects/fp6_imagen.html (2016-01-29)
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  • CNG - PROGRAMMES
    BELL John Professor Tel 44 1865221340 Email Contact Organisation THE CHANCELLORS MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD OXFORD CENTRE FOR DIABETES ENDOCRINOLOGY AND METABOLISM OCDEM NUFFIELD DEPARTMENT OF CLINICAL MEDICINE University Offices Wellington Square UNITED KINGDOM Project description Epidemiologists clinical trialists and experimental scientists are confronted with a wealth of potential opportunities for molecular phenotyping large numbers of biological samples obtained from cohorts patients or animal models The challenge now is to ensure that these tools are developed to permit high throughput analyses of significant numbers of samples cohort protocols are in place for sample collection and storage and that systems are in place to capture warehouse and analyse the range of biolog ical data that will emerge from these studies This consortium will bring some of these tools into practice during the course of the next four years so that they can be used to identify biomarkers that predict disease determine risk and relate to disease activity or response to therapy The programme is divided into three parts The evaluation of sample collection and storage methodology to optimally sample variation and disease analyte stability The development of tools for molecular phenotyping at epidemiologic scale including measuring small molecules metabonomics mRNA in white blood cells transcription profiling protein and peptide analysis using mass spectrometry methodology affinity arrays and tissue arrays DNA methdylation patterns and genetics The development of bioinformatic tools for data warehousing data interrogation and statistical analysis in large sample sets The consortium will adopt two separate approaches genome wide systematic methodology metabonomics ms based metanomics and limited analysis using sets of candidate biomarkers transcipt profiling methylation affinity arrays tissue arrays Collectively these programmes bring together the necessary skills and tools to allow moleculear phenotyping to be realistically applied informing our study of common disease and its

    Original URL path: http://www.cng.fr/en/projects/fp6_molpage.html (2016-01-29)
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  • CNG - PROGRAMMES
    coop PHENOGENE MOLTOOLS Advanced molecular tools for array based analyses of genomes transcriptomes proteomes and cells Coordinator Contact Person LANDEGREN Ulf Professor Tel 46 184714910 Fax 46 184714808 Email Contact Organisation UPPSALA UNIVERSITET DEPARTMENT OF GENETICS AND PATHOLOGY St Olofsgatan 10B PO Box 256 SWEDEN Project description The recording of complete genome sequences provides for the first time opportunities to comprehensively characterize the flow of information from genetic variation at the DNA level over messages expressed as RNA and on to their protein products and to functions of the cell By eavesdropping on these processes it will be possible to identify genetic variation underlying malignancy diabetes and other common diseases and to monitor and ultimately explain molecular processes involved in these and other important conditions Recent years have seen rapid growth of techniques for high throughput analyses of genes transcripts proteins and cells using microarrays but current methods still capture only a small fraction of the information embodied in the molecules This project brings together leading European laboratories and one US lab The purpose is to build an infrastructure to develop a next generation toolbox for large scale molecular analyses in the following six interrelated analytical modes parts of whole genomes will be rapidly scanned for any alterations extensive sets of genetic variants will be traced in large numbers of individuals patterns of gene expression will be recorded at unprecedented quantitative and sequence resolution expression and interactions of large sets of proteins will be measured in array formats novel molecular tools will enable analyses at the ultimate level of single DNA RNA or protein molecules and arrays of viable cells will permit extensive functional analyses to characterise complex processes in high throughput The suite of microarray based technologies developed in the course of this program will be of strategic value

    Original URL path: http://www.cng.fr/en/projects/fp6_moltools.html (2016-01-29)
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