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.
Coordinator
Karolinska Institutet (Sweden)
Other participants
ALMA MATER STUDIORUM-UNIVERSITA DI BOLOGNA
- Centro Interdipartimentale “Luigi Galvani” per Studi Integrati di Bioinformatica, Biofisica e Biocomplessità - CIG
- Resp. Scientifico : Prof. Claudio Franceschi
The University Of Edinburgh (UK)
Universitè Paris Diderot - Paris 7 (France)
King'S College London (UK)
Università Degli Studi Di Milano (Italy)
Academisch Ziekenhuis Leiden - Leids Universitair Medisch Centrum (Netherlands)
Gatc Biotech Ag (Germany)
Centre National De La Recherche Scientifique - CNRS (France)
University College London (UK)
Acureomics Ab (Sweden)
Acure Pharma Ab (Sweden)
Yecuris Corporation (USA)
Pronexus Analytical Ab (Sweden)
Dr David Hay Fibromed Ltd (UK)
Genedata Ag (Switzerland)
Nestle Institute Of Health Sciences Sa – NIHS (Switzerland)
Start date 01/10/2013
End date 30/09/2018
Duration 60 months
Project Reference 602757
Project cost 17.047.936,40 EURO
Project Funding 11.994.549 EURO
Area FP7-COOPERATION-HEALTH
Subprogramme Area HEALTH.2013.2.1.1-1: Functional validation in animal and cellular models of genetic determinants of diseases and ageing processes
Contract type Collaborative project