Decoding Gαi Regulation Mechanisms in Heart Diseases

Project Summary

G protein-coupled receptors (GPCRs) constitute a large family of proteins responsible for transmitting signals from outside to inside the cell. They play a key role in numerous biological processes and are the target of nearly 40% of medications. GPCRs activate G proteins, triggering complex signaling pathways that affect various systems in the body, including the cardiovascular system. Most current treatments target the sympathetic nervous system, but the parasympathetic system, which slows the heart via the G_αi protein, is less studied. One strategy is to directly target the regulation of G_αi. Through RGS4 and RGS6 are two proteins that modulate G_αi activity. By studying the interactions between RGS4, RGS6, and G_αi using NMR techniques, we hope to gain insights into the structural changes within these complexes to exploit them for therapeutic purposes.

Research Approach
The project will involve:

• Expression of Gαi, and RGS4/6 in E. coli, with isotopic labeling (¹⁹F, ¹⁵N, ¹³C)
• Purification using affinity, size-exclusion, and other chromatographic methods
• Structural and dynamic analysis using nuclear magnetic resonance (NMR) spectroscopy

This work will contribute to a better understanding of Gαi’s regulatory mechanisms and identify potential targets for therapeutic intervention.

Laboratory & Environment
The selected candidate will join the laboratory of Dr. Louis-Philippe Picard, equipped for state-of-the-art protein production and NMR spectroscopy. The lab is located at the Institut de Pharmacologie de Sherbrooke (IPS), a dynamic and multidisciplinary research environment offering cutting-edge facilities and collaborative opportunities.
Learn more: https://www.usherbrooke.ca/ips/

Candidate Profile
We are seeking a motivated and detail-oriented candidate with:

• A B.Sc. or M.Sc. in biological sciences or chemistry (biochemistry, molecular and cellular biology, biotechnology, pharmacology, etc.)
• A strong academic record
• Experience in protein purification and/or NMR spectroscopy (an asset, but not required)
• A genuine interest in structural biology