New GPCR-Specific Biosensor Technology to Monitor Cellular Events Associated with Drugs Efficacy and Side Effects

Challenge: G protein-coupled receptors (GPCRs) form the largest family of cell surface receptors involved in signal transduction of many hormones and transmitters. It follows that drugs targeting GPCRs represent close to 40% of all drugs on the market today. Recent discoveries regarding their function and mechanism of action help pave the way for the development of more selective therapeutics for different clinical indications. However, more sophisticated tools to dissect their intricate signaling networks are needed.

Solution: The team has developed and validated a high-throughput drug screening toolkit consisting of more than 40 cell-based biosensors to simultaneously monitor the various signaling pathways engaged by GPCRs upon ligand binding. The technology, based on bioluminescence resonance energy transfer (BRET), provides a direct measure of molecular activation and interactions inside living cells. This approach pioneers a timely shift from the current single function assay to a more rapid and informative multidimensional platform for GPCR screens. Predictions from these studies can be further tested in pre-clinical ex vivo and in vivo models to elucidate complex signalling pathways that will enable the development of drugs with improved efficacy profiles and fewer side effects.

Achievements/Impact: The project led to the validation of a panel of biosensors broadly covering the GPCR signaling repertoire including heterotrimeric and monomeric G proteins, second messengers, protein kinases and ion channels. Two CQDM pharma members have in-licensed the technology for their drug discovery programs. In 2013, the technology was licensed to Domain Therapeutics, who created a subsidiary in Montreal called Domain Therapeutics North America (DTNA) to monetize the BioSens-AllTM platform. DTNA has already executed research contracts with more than 15 pharma organizations, biotech and academic groups in North America, Europe and Japan.

Principal Investigator:

Michel Bouvier
Université de Montréal


Terence Hébert, Stéphane Laporte
McGill University

Richard Leduc
Université de Sherbrooke

Graciela Pineyro
Université de Montréal

Jean-Claude Tardif,
Eric Thorin

Montreal Heart Institute

Completed Project
$1,827,000 / 3 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer