Development and validation of BRET-based biosensors for drug candidate profiling

G protein-coupled receptors (GPCRs), which are proteins normally found at the surface of cells, are involved in regulating virtually every physiological response. GPCRs activate numerous intracellular signaling mechanisms and are the targets of more than 30% of today’s prescribed drugs. These drugs have traditionally been thought to act as on/off switches to activate or inhibit GPCR activity, but recent findings indicate that they also promote alternative and sometimes deleterious responses. This notion opens avenues for the development of drugs with better efficacies and fewer side effects by selectively targeting the therapeutically relevant responses. However, tools to study the full spectrum of GPCR signaling are still lacking. Using a biophysical approach called BRET (bioluminescence resonance energy transfer) to measure the extent of GPCR activation, the project will establish novel experimental and analytical methods to probe the different modalities of GPCR signaling and to make better predictions about the efficacy and safety of new drugs targeting GPCRs. The post-doctoral fellows involved in the project will develop and validate these new tools under the co-supervision of industrial and academic mentors and the results of the project will be transferred to our industrial partner for inclusion in on
going drug discovery programs.

Faculty Supervisor:

Richard Leduc;Terry Hébert;Stéphane Laporte;Michel Bouvier;Graciela Pineyro

Student:

Partner:

Domain Therapeutics NA Inc

Discipline:

Life Sciences

Sector:

Professional, scientific and technical services

University:

McGill University; Research Institute of the McGill University Health Centre; Université de Montréal; Université de Sherbrooke

Program: