Objectif "Blood vessels pervade all tissues in the body to supply nutrients and oxygen. Aberrant vessel growth and function are hallmarks of cancer and cardiovascular diseases and they contribute to disease pathogenesis. Antiangiogenic therapeutics have reached the clinic, but limited efficacy and resistance raise unresolved challenges. The current limitations of angiogenic medicine call for a more integrated understanding of the angiogenic process that focuses not only on the instigators of vessel branching but also on mechanisms that sustain vessel growth. Recent insights into fundamental aspects of cell growth move metabolism into spotlight and establish how proliferating cells reprogram their metabolism to provide energy and building blocks for cell replication. During angiogenesis, endothelial cells (ECs) also convert between growth states: although mostly quiescent in adult tissues, ECs divide and migrate rapidly upon angiogenic stimulation. To allow growth of new vessel branches, ECs therefore need to adjust their metabolism to increase energy production and biosynthetic activity. However, the molecular mechanisms that coordinate EC metabolism with angiogenic signalling are not known to date. In this proposal, we put forth the hypothesis that metabolic regulation is a key component of the endothelial angiogenic machinery that is required to sustain vessel growth. Thus, this proposal aims (I) to define transcriptional circuits that link EC growth with metabolism, (II) to explore the regulation of these transcriptional networks by lysine acetylation, a nutrient-regulated protein modification with key functions in metabolism, and (III) to assess the role of sirtuin deacetylases for sensing endothelial energetics during vascular growth. Understanding the principles of angiogenesis-metabolism crosstalk will not only yield novel insights into the basic mechanisms of vessel formation but will also provide unprecedented opportunities for future drug development." Champ scientifique medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicinecardiologycardiovascular diseasesmedical and health sciencesclinical medicineoncologymedical 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-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2012-StG_20111109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Contribution de l’UE € 1 487 920,00 Adresse HOFGARTENSTRASSE 8 80539 Munchen Allemagne Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Contact administratif Schreiner Angela (Mrs.) Chercheur principal Michael Potente (Dr.) 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 MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Allemagne Contribution de l’UE € 1 487 920,00 Adresse HOFGARTENSTRASSE 8 80539 Munchen Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Contact administratif Schreiner Angela (Mrs.) Chercheur principal Michael Potente (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée