Objectif
Recently intense research identified around 4,000 single nucleotide polymorphisms (SNPs) associated with human age related diseases such as metabolic disorders. Despite their highly significant association to pathology, the functional role of these genetic variants is, in most cases, yet to be elucidated. The evolutionary distance of most animal models from humans represents a major limitation for the functional validation of these SNPs. To overcome these difficulties, HUMAN will generate mouse models carrying human hepatocytes or pancreatic βcells from either primary cells (hepatocytes) or induced pluripotent stem cells (iPSCs). This innovative approach offers the unique possibility of studying function of genetic risk variants associated with metabolic diseases in an integrated living system (the mouse body), but within human-derived organs, i.e. liver and pancreas. iPSCs used to generate hepatocytes and βcells will derive from extreme phenotypes, i.e. patients affected by severe metabolic diseases such as type 2 diabetes (T2D) or subjects selected for exceptional healthy longevity (subjects over 105 years and offspring of nonagenarian sibships) all fully clinically and metabolically characterised and genotyped; they will be selected according to the best combination of risk and protective alleles. We will test the effect of different nutritional regimes (e.g. high fat diet, caloric restriction), to disentangle the complex molecular mechanisms and circuitry across organs (e.g. hypothalamus-liver axis) which lead to pathology. HUMAN associates a core of outstanding basic research institutions to leading European biotech SMEs, and has the capability to produce at least 500 humanised mice. HUMAN will generate iPSCs biobanks and comprehensively manage all associated information. HUMAN is uniquely situated to drive innovation towards a better knowledge of the genetic basis of human metabolic diseases, thereby contributing to healthier aging of European citizens.
Champ scientifique
Appel à propositions
FP7-HEALTH-2013-INNOVATION-1
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Régime de financement
CP-IP - Large-scale integrating projectCoordinateur
17177 Stockholm
Suède
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Participants (15)
75794 Paris
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20122 Milano
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2333 ZA Leiden
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WC2R 2LS London
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40126 Bologna
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WC1E 6BT LONDON
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EH8 9YL Edinburgh
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F-75205 / 13 Paris
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SE-90187 Umeå
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Participation terminée
756 43 UPPSALA
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97223 TIGARD OREGON
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78467 Konstanz
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17177 STOCKHOLM
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4053 BASEL
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1015 LAUSANNE
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