Dr Mohammed Ayoub

From

King Saud University - SA

In residence at

Physiology of Reproduction and Behaviour (PRC) / Centre INRAE Val de Loire, CNRS, University of Tours, IFCE - FR

Host scientist

Dr Eric Reiter

PROJECT

Development and characterization of a new generation of GPCR therapeutics.

This project aims to develop a new generation of therapeutics based on specific antibodies (nanobodies), which specifically modulate the function of G protein-coupled receptors (GPCRs). GPCRs currently accounts for 30 to 40% of the currently marketed drugs and are centrally involved in most physiological and pathological processes. This is an ambitious project to help build the outstanding scientific and technical environment necessary for the generation, functional screening and pharmacological profiling of various GPCR-selective nanobodies both in vitro and in vivo. Indeed, in order for the laboratory to succeed in this endeavour, it is crucial to be able to rely on the cutting-edge technologies in the field. Therefore, considerable effort will be devoted to develop and set up the new technologies and assays needed such as bioluminescence resonance energy transfer (BRET), homogeneous time-resolved fluorescence (HTRF), fluorescence, signaling assays and others. It will also be essential to address the different aspects of the project in the context of the newly emerged concepts in molecular pharmacology including heteromerization, multiple coupling, biased signalling…etc. Of course, this requires the appropriate expertise of the research staff as well as strong collaborations with many national and international academic and industrial laboratories. Importantly, at UMR 7247 PRC, the work will involve close collaboration between the BIOS and DRUGS research groups as well as with Synthelis, a biotech startup. Their collective expertise in GPCR pharmacology, molecular simulation and modelling, antibody generation and selection, GPCR expression, production and reconstitution in acellular systems is complementary and innovative. The ultimate objective being to develop novel drug candidates, so it is essential to setup the appropriate in vivo models. To address this need, the selected GPCR-modulating nanobodies are tested for their potential therapeutic action using various preclinical models established in collaborations with several research units within region Centre. This research project is imbedded in the activities of the MabImprove labex, which is devoted to therapeutic antibodies. This provides an outstanding research environment in the key domains such as immunology and antibody engineering.