Objective G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors in eukaryotes. They bind a wide range of ligands, such as neurotransmitters, hormones, lipids and many others. GPCRs are the target of more than 30% of the drugs currently on the market, addressing neuropsychiatric, cardiovascular, pulmonary and metabolic disorders, cancer, obesity and AIDS. The functional versatility of GPCRs cannot be explained by a simple two-state model of activation considering only an active and an inactive state, as these receptors are highly dynamic and can explore a wide range of conformations. Some receptors of the family can signal in the absence of ligand (basal activity), and despite GPCR have been largely studied in the past years, little is known about their signal transduction mechanism. Apart from ligands and signalling partners, the structure and function of GPCRs can be modulated by lipids. In this context, our research will be divided in two steps: delineating the role of lipids on GPCR conformational landscape at the molecular scale (Aim1) and exploring an additional allosteric factor in line with lipid composition, the homo- and hetero-receptor oligomerisation (Aim2). To that purpose, we will apply an integrated, multidisciplinary analysis, to characterize protein dynamics under physiological conditions, with the GPCR reconstituted in model lipid systems or living cells, and in the presence of ligands, signalling and regulatory partners. We will use conformational probes to investigate the effect of lipids and other GPCRs on receptor dynamics, and correlate these findings with functional properties such as agonist binding and G protein coupling. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVmedical and health sciencesclinical medicineoncologymedical and health scienceshealth sciencesnutritionobesity Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2017 - Individual Fellowships Call for proposal H2020-MSCA-IF-2017 See other projects for this call Funding Scheme MSCA-IF-GF - Global Fellowships Coordinator UNIVERSITE DE MONTPELLIER Net EU contribution € 246 668,40 Address 163 RUE AUGUSTE BROUSSONNET 34090 Montpellier France See on map Region Occitanie Languedoc-Roussillon Hérault Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 246 668,40 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY United States Net EU contribution € 0,00 Address SERRA MALL 450 94305 2004 Stanford See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 160 130,40
