Grant: Foundation Grant

Many hormones and transmitters have their biological effects by modulating the activity of receptors located at the surface of cells. Among these, G protein-coupled receptors (GPCR) represent the largest family of protein involved in transferring information from the outside to the inside of the cells. With more than 800 members, GPCR control many distinct physiological functions such as neurotransmission, cardiac contraction, vascular tone, endocrine secretion, metabolism, etc.... As a consequence, they represent privileged targets for the development of drugs for many distinct clinical indications. It is estimated that more than 30% of the current prescription drugs act through GPCR. Yet, only a limited fraction of the therapeutic potential of GPCR has been exploited to date. Many receptors with important roles have not yet been targeted and new developments in molecular pharmacology and structural biology offer new opportunities for the development of drugs with greater therapeutic efficacies and less undesirable effects. In particular, new tools allowing to unravel their structures and to monitor their signaling activities with unprecedented sensitivity and spatiotemporal resolution open the perspective of developing new drugs based on an intimate understanding of their mode of action at the molecular level. Therefore, the present proposal aims at further understanding the molecular mechanisms controlling GPCR activity, with the intention of identifying novel processes that could be pharmacologically targeted for therapeutic purposes. The studies proposed also include the search for new chemical entities that will serve as tools to better probe receptor functions and could represent interesting lead candidates for the development of new drugs classes for unmet clinical needs.