The Julius Axelrod Award in Pharmacology is a prestigious honor presented not just for significant contributions to understanding the biochemical mechanisms underlying the pharmacological actions of drugs, but also for significant contributions to the continuing mentorship of other pharmacologists. This year’s lecturer was Michel Bouvier PhD, from the University of Montreal, who just so happens to have only 2 degrees of separation from Julius Axelrod himself! Not only has Dr. Bouvier contributed amazing research to the scientific community, which I will attempt to summarize below, but he has also helped train 33 PhD students and over 30 post-docs during his career.
His talk, entitled “Unraveling the molecular and structural determinants of GPCR functional selectivity; potential for drug discovery” or as he described it “shining new light on G protein-coupled receptor functional selectivity;…and a few more things”, focused on a common problem in GPCR research (which you might have guessed from the title): the determination of functional selectivity.
His research uses biosensor based profiling, which they developed as a signaling detection platform in order to monitor the activity of different pathways associated with GPCRs. Among other discoveries, their use of Enhanced Bystander (ebBRET) allows for spatiotemporal monitoring of translocation and signal propagation, and can monitor the receptor during different stages including loss at the plasma membrane and its journey through the endosomal pathway. Other models include the identification of compounds by clusters to create a signaling signature that can, among other things, help predict off target side effects of different drugs, which is especially important considering the pluri-dimensional nature of GCPR signaling.
Overall, the strategies they have developed can help identify novel signaling pathways important for therapeutic development and can lead toward the development of safer drugs in the future, two key features important for the future of personalized medicine.