Health and the understanding of metabolism, aging and nutrition

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Project Title: Health and the understanding of metabolism, aging and nutrition
Project Number: CORDIS-110177
Project web address: Follow on CORDIS
Organization: Karolinska Institutet, Sweden, Stockholm
Collaborators: University Of Edinburgh, GB
University College London, GB
King'S College London, GB
Centre National De La Recherche Scientifique (Cnrs), FR
Università Degli Studi Di Milano, IT
Academisch Ziekenhuis Leiden, NL
Genedata Ag, CH
Alma Mater Studiorum - University Of Bologna, IT
Gatc Biotech Ag, DE
Universite Paris Diderot - Paris 7, FR
Acureomics Ab, SE
Nestle Institute Of Health Sciences Sa, CH
Acure Pharma Ab, SE
Pronexus Analytical Ab, SE
Yecuris Corporation For Profit Corporation, US
Principal Investigators (PI): Angela Noble, GB
Paul Labett, GB
Anne-Sophie Refloc'H, FR
Sergio Longo, IT
Natascha Ostrowski, DE
Timo Wittenberger, CH
Paul Nichols, CH
Kamila Kolasinska, GB
Brice Kerber, FR
Johan Trygg, SE
Torbjörn Lundstedt, SE
Jan Kehr, SE
John Bial, US
Mario Soffritti, IT
Jacobus De Graaf, NL
Therese Lind, SE
Project Description:
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 βcells 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 βcells 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.
Project Terms:
life sciences