Project Description
The urotensinergic system, composed of a G protein-coupled receptor (UT) and two endogenous ligands, has garnered significant attention due to its involvement in the initiation and/or the evolution of various cardiovascular diseases. Unfortunately, despite a proven efficacy in various animal models, initial clinical investigation of candidate UT antagonists showed limited efficacy in humans. Failure to appreciate 1) the impact of interspecies variability, 2) to consider potential biased agonism and possible probe-dependent action of UT antagonists at the preclinical stage probably contributed to these translational failures. This system remains to be exploited therapeutically. However, the development of effective ligands remains complicated due to our limited understanding of downstream ligand-receptor-effector interactions and the impact of interspecies variability. The objectives of this doctoral project are therefore to:
- Develop new peptidic ligands/biased agonists/allosteric modulators targeting UT.
- Identify the structural and physico-chemical determinants responsible for their biological activities (probe-dependent effect, biased agonism, etc.).
- Study the phenotypic responses of the latter in a model of human cells (cardiomyocytes derived from induced pluripotent cells (iPSCs-CMs) – collaboration with Pr. Hébert, McGill University).
Research Areas
- Medicinal Chemistry
- Pharmacology
- Cellular and Molecular Biology
Research Supervisor
- David Chatenet, Professor
- Terence E. Hébert, Professor (McGill university)
- Juliana Dallagnol, Research Associate
Study Programs
This study project will be carried out under the following program: Ph.D. in Biology (French description)
Desired Profile
- Hold a master’s degree in biology, biochemistry, pharmacology, chemistry, or a related research field;
- Be open to collaborating with an interdisciplinary team working in different research areas;
- Have a curious, resourceful, and autonomous mindset;
- Have a good fluency on both French and English.
Applicants with knowledge or experience in some or all of the following areas are encouraged to apply:
- GPCR pharmacology
- Organic/peptidic synthesis
- Compounds purification using various chromatographic methods
- Cell biology
Financial Support
INRS offers many scholarship programs (in french). Every student will benefit from a scholarship during their higher education studies.
Location
Centre Armand-Frappier Santé Biotechnologie
531, boulevard des Prairies
Laval (Québec) H7V 1B7
How to apply
Interested persons can submit their application in a single PDF file by using the online form.
The application must include:
- Motivation letter describing their research interests
- Complete CV
- a statement of all your academic transcripts
- The name of three contact information for further reference.
We encourage women, visible minorities, ethnic minorities, aboriginals and people with disabilities to apply.