Doctoral studies in molecular biology or biochemistry
The Montreal Clinical Research Institute’s (IRCM) Molecular Physiology Research Unit, headed by Dr. Mathieu Ferron, is seeking to recruit at least one PhD student to carry out exciting projects on the role of the post-translational modification gamma-carboxylation in pancreatic beta cell function and in diabetes.
Gamma-carboxylation targets glutamic acid residues, occurs in the endoplasmic reticulum (ER) and affects the function of secreted proteins. Our group recently discovered that gamma-carboxylation prevents beta cell dysfunction (Cell Reports 2023). We have identified endoplasmic reticulum Gla protein (ERGP) as a novel gamma-carboxylated ER-resident Ca2 -binding protein expressed in beta cells. Our findings suggest that gamma-carboxylated ERGP protects cells against Ca2 overfilling by restraining store-operated Ca2 entry (SOCE).
Our current aim is to decipher the molecular and cellular mechanisms by which ERGP and its gamma-carboxylation regulate calcium flux and insulin secretion in mouse and human beta cells. In addition to ERGP, we have discovered several new gamma-carboxylated proteins in beta cells, which are possibly involved in protein folding and quality control in the ER. Therefore, we are also seeking to understand how gamma-carboxylation intersects with the protein folding machinery in the ER. Our long-term goal is to identify new potential targets for the treatment or prevention of type 2 diabetes.
This project is funded by the Canadian Institutes of Health Research (CIHR). The Ferron laboratory has an internationally recognized expertise in the molecular mechanisms of metabolic diseases.
Recent key publications from our laboratory on gamma-carboxylated proteins:
Novel Function of Vitamin K-Dependent Carboxylation in Beta-Cells and Diabetes. Trends Endocrinol Metab. 2024. (PMID: 38429160)
Vitamin K-dependent carboxylation regulates Ca2 flux and adaptation to metabolic stress in beta-cells. Cell Reports. 2023. (PMID: 37171959)
The half-life of the bone-derived hormone osteocalcin is regulated through O-glycosylation in mice, but not in humans. eLife. 2020. (PMID: 33284103)
VKOR paralog VKORC1L1 supports vitamin K-dependent protein carboxylation in vivo. JCI Insight. 2018 (PMID: 29321368)
Proprotein convertase furin regulates osteocalcin and bone endocrine function. J Clin Invest. 2017 (PMID: 28972540)
Summary of responsibilities
The project will take advantage of a broad range of approaches to uncover the cellular, molecular, and physiological functions of ERGP and gamma-carboxylation in beta cells. The PhD student will need to master and/or be willing to learn basic molecular and cell biology methods such as molecular cloning, cell culture, immunoprecipitation and immunoblot techniques, and microscopy (Ca2 imaging, FRET, etc.). This project will also require proteomics analyses (e.g. BioID, post-translational modifications, etc.) and the use of genetically engineered mouse models. Important findings will be further validated using human pancreatic islets. Under the supervision of the lab director (Dr Ferron), the PhD student will be responsible for independently designing and executing experiments, analyzing data, presenting results at laboratory meetings and conferences (local and international), and writing manuscripts for publication in scientific journals. In-person work is mandatory for this position.
Financial support
28 000 CAD/year (minimum).
The IRCM is located at the corner of rue St-Urbain and avenue des Pins, near downtown and Plateau Mont-Royal. The Place-des-Arts (green line) and Sherbrooke (orange line) metros are a 10-minute walk away. We are connected by several bike paths, including those on rue St-Urbain and avenue des Pins. We have secure bicycle parking. The IRCM is an autonomous, not-for-profit research institution, affiliated with the Université de Montréal and associated with McGill University. All IRCM researchers hold university appointments at the Université de Montréal, and most research directors are also associate members of McGill University. Located in the heart of Montreal's academic community, the IRCM attracts the best researchers. Every year, more than a hundred master's and doctoral students, as well as some fifty postdoctoral fellows, supervised by experienced researchers in various fields of biomedical research, come to improve and/or polish their scientific training at the Institute.
The training of students, trainees and employees is an integral mission of IRCM and of Ferron Laboratory, and we aim to attract and retain the best scientists. We have a dedicated academic affairs team with the primary mission of providing a respectful work environment and supporting all members of the IRCM community. IRCM's Code of Collegial Conduct clearly specifies that respect for people and gender equality is a core value of our institution, and we recognize diversity as a strength and a source of richness. IRCM and the Ferron Laboratory strives to provide an environment that promotes and supports the inclusion and fair representation of women, members of the LGBTQ community, people living with disabilities and people from ethnic, cultural, and religious minorities.
Qualifications required
Undergrad (licence) and/or Master degree in Biochemistry or Molecular Biology (or related field) with good GPA;
Very strong interest in research and discovery;
Previous experience in research laboratories is an asset;
Independence, autonomy and productivity in laboratory experiments; ability to generate new research hypothesis;
Fluency in English (written and verbal);
The Ferron laboratory is a respectful, friendly, and non-discriminatory working environment. This behavior is required from the candidate.