Objectif "Elevated levels of circulating LDL-cholesterol are a major determinant contributing to atherogenesis and coronary artery disease. Therefore, many studies address the central transcriptional pathways that regulate cholesterol metabolism. However, transcriptional regulation does not allow cells to quickly adapt to the cholesterol fluxes that they encounter. For this, rapid and reversible post-transcriptional modifications are used, in conjunction with transcriptional control. Ubiquitylation - the post-transcriptional conjugation of ubiquitin to proteins – is studied in relation to many cellular processes. Much less is known about the contribution of the ubiquitin-proteasomal-system (UPS) to regulation of lipid metabolism and development of cardiovascular disease.I recently identified the E3-ubiquitin ligase IDOL as a novel post-transcriptional regulator of the LDLR pathway. My lab also recently identified two genes, the E3-ubiquitin ligase MARCH6 and the de-ubiquitylase USP2, for which no role in sterol metabolism was known, as important regulators of cellular cholesterol metabolism. With IDOL, these genes control key nodes of cholesterol synthesis and uptake and represent previously unrecognized mechanisms to control cholesterol homeostasis. To study the contribution of these genes to cholesterol metabolism, we will use state-of-the-art mutant mouse models, in vitro assays, and a unique collection of dyslipidemic patient material. Our goal is to characterize the contribution of these genes to cholesterol homeostasis and to examine their involvement in the development of dyslipidemia and atherosclerosis.Investigating these novel regulatory systems will provide important mechanistic insight into the contribution of the UPS to cholesterol metabolism in health and disease. As components of the UPS are amenable to pharmacological manipulation these studies could potentially lead to novel targets for treatment of hypercholesterolemia and coronary artery disease." Champ scientifique medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinephysiologyhomeostasis 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-CG-2013-LS4 - ERC Consolidator Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2013-CoG Voir d’autres projets de cet appel Régime de financement ERC-CG - ERC Consolidator Grants Institution d’accueil ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Contribution de l’UE € 1 999 998,00 Adresse MEIBERGDREEF 15 1105AZ Amsterdam Pays-Bas Voir sur la carte Région West-Nederland Noord-Holland Groot-Amsterdam Type d’activité Higher or Secondary Education Establishments Chercheur principal Noam Zelcer (Dr.) Contact administratif Gulseren Yalvac (Ms.) 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 MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Pays-Bas Contribution de l’UE € 1 999 998,00 Adresse MEIBERGDREEF 15 1105AZ Amsterdam Voir sur la carte Région West-Nederland Noord-Holland Groot-Amsterdam Type d’activité Higher or Secondary Education Establishments Chercheur principal Noam Zelcer (Dr.) Contact administratif Gulseren Yalvac (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée