Objectif The ability to generate pluripotent stem cells (iPSC) by reprogramming somatic tissues is arguably the greatest breakthrough in biomedical science of the last decade. The most inaccessible cells of the body can now be derived repeatedly from any individual. This could have a huge impact on understanding disease and the development of new therapeutic drugs but it will require a new level of sophistication in bioassays to create disease models and monitor disease phenotypes. The project I propose here will take up this challenge for the cardiovascular system, creating new human models of heart failure and vascular disease that presently do not exist. My group is uniquely positioned in Europe to realize these ambitions through more than a decade of research on cardiac and vascular cells from human embryonic stem cells and more recently hiPSC; its present location in Leiden University Medical Centre is optimal for fostering clinical links. My group is one of few worldwide that uses conventional homologous recombination in human PSCs. My aims here are (1) develop protocols for differentiating all cells of the heart (2) engineer synthetic and native human myocardium that models healthy tissue and common disease states and (3) generate sets of isogenic diseased hPSC to model pathogenesis. This will be realized by deriving lineage marked “rainbow coloured” reporter hPSC lines, introducing selected (immature) cardiovascular cells into engineered constructs and subjecting them to mechanical/biochemical stress factors like cyclic contraction and fluid flow that would normally induce maturation and disease. The constructs will support simultaneous measurement of functional tissue parameters and include hiPSC from relevant diseases, genetically or pharmacologically rescued and isogenic hESC with the corresponding gene mutations. These new “sick human heart” and “ diseased vessel” models and novel bioassays will significantly advance technology to have major impact on the field. Champ scientifique medical and health sciencesclinical medicineangiologyvascular diseasesmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicinecardiology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Appel à propositions ERC-2012-ADG_20120314 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil ACADEMISCH ZIEKENHUIS LEIDEN Contribution de l’UE € 2 500 000,00 Adresse ALBINUSDREEF 2 2333 ZA Leiden Pays-Bas Voir sur la carte Région West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Type d’activité Higher or Secondary Education Establishments Contact administratif Liesbeth Dorama (Mrs.) Chercheur principal Christine Lindsay Mummery (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire ACADEMISCH ZIEKENHUIS LEIDEN Pays-Bas Contribution de l’UE € 2 500 000,00 Adresse ALBINUSDREEF 2 2333 ZA Leiden Voir sur la carte Région West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Type d’activité Higher or Secondary Education Establishments Contact administratif Liesbeth Dorama (Mrs.) Chercheur principal Christine Lindsay Mummery (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée