Objective
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.
Fields of science
Call for proposal
FP7-HEALTH-2013-INNOVATION-1
See other projects for this call
Funding Scheme
CP-IP - Large-scale integrating projectCoordinator
17177 Stockholm
Sweden
See on map
Participants (15)
75794 Paris
See on map
20122 Milano
See on map
2333 ZA Leiden
See on map
WC2R 2LS London
See on map
40126 Bologna
See on map
WC1E 6BT LONDON
See on map
EH8 9YL Edinburgh
See on map
F-75205 / 13 Paris
See on map
SE-90187 Umeå
See on map
Participation ended
756 43 UPPSALA
See on map
97223 TIGARD OREGON
See on map
78467 Konstanz
See on map
17177 STOCKHOLM
See on map
4053 BASEL
See on map
1015 LAUSANNE
See on map