Grant: Operating Grant

Chemical transmission is a common mechanism used by cells to communicate. It consists in the liberation, by the transmitting cells (neuronal or endocrine cells), of chemically encoded messages (neurotransmitters or hormones) that are selectively recognized and decoded by receptor devices located on the surface of effector cells. The largest class of such receptors is known as the G protein-coupled receptor (GPCR) family with several hundred members involved in a wide variety of physiological processes. Dysfunctions of these receptors have been shown to be involved in the development and the complications accompanying various pathological states. They thus represent major pharmacological targets for the development of new drugs candidates with potential applications in all clinical fields. In fact, more than 50% of the drugs prescribed today act by activating or blocking a GPCR. Although significant progress has been made in the last 20 years regarding the structure and mechanisms of action of the GPCRs, our understanding of how drugs promote biological responses through their interaction with these receptors is still rudimentary. Here we propose, using a combination of molecular, biochemical, biophysical and pharmacological approaches, to further investigate the mechanisms underlying drug action through GPCRs. In particular, we will focus on the process controling selectivty , with the objective of developping new therapeutics with better efficacy and selectivity profiles.