Blood–Brain Interface of Omega‑3 Fatty Acids

This research project aims to understand how apolipoprotein E (APOE) genotypes, particularly the ε4 allele, modify the metabolism and transport of long‑chain polyunsaturated fatty acids (LC‑PUFAs) such as DHA, EPA, and ARA between organs and into the brain. These essential dietary lipids play a crucial role in membrane fluidity, regulation of gene expression, and proper neuronal function. APOE is a key protein involved in lipid transport, and its isoforms (APOE2, APOE3, APOE4) differentially affect lipid homeostasis. APOE4 carriers exhibit altered lipid metabolism, reduced brain DHA levels, and increased vulnerability to neurodegenerative diseases.

Our central hypothesis is that APOE4 disrupts omega‑3 LC‑PUFA homeostasis, leading to altered lipid fluxes and physiological dysfunction across multiple organs. To test this hypothesis, we will trace ^13C‑labeled LC‑PUFAs from the bloodstream to the brain and develop a multi‑organ model to better understand systemic lipid dynamics.

Objective 1: Develop and validate a GC‑MS/MS method to quantify ^13C‑labeled LC‑PUFAs and their metabolites in tissues. This approach will enable precise tracking of lipid transport and transformation, complementing classical lipidomic analyses.

Objective 2: Investigate how APOE genotype influences LC‑PUFA metabolism across brain barriers. Using transgenic mice expressing human APOE isoforms, we will analyze sex‑ and genotype‑specific differences in lipid absorption, distribution, and conversion into bioactive mediators.

Objective 3: Build a multi‑organ pharmacokinetic model (LIMOS) to simulate lipid flux and metabolism between organs. This model will integrate tracer data and biological parameters to predict lipid behavior as a function of genotype and sex.

This interdisciplinary research program combines lipidomics, tracer studies, and computational modeling to advance our understanding of lipid transport and metabolism. It will generate high‑impact publications, train students in both biological and quantitative sciences, and pave the way for targeted interventions aimed at restoring lipid balance in populations at risk of cognitive decline.

Contrat doctoral

Annual salary of CAD $27,000 per year, and a minimum of two international conferences fully funded during the PhD program.

Research Center on Aging – Université de Sherbrooke

The laboratory is at the forefront of research on brain aging and the role of omega‑3 fatty acids in cognitive health. Our team is among the very few worldwide to use uniformly ^13C‑labeled omega‑3 fatty acids, a cutting‑edge approach that enables exceptionally precise investigation of their kinetics and metabolism, both in the context of aging and in carriers of the APOE ε4 allele, a major risk factor for cognitive decline and Alzheimer’s disease. This work has resulted in numerous international publications (Plourde et al., 2011, 2014; Chouinard‑Watkins et al., 2013; Léveillé et al., 2017).

In parallel, the laboratory has developed recognized expertise in APOE4 animal models to further investigate omega‑3 metabolism and assess the impact of omega‑3‑enriched diets on cognitive decline. These studies have demonstrated significant neuroprotective effects, reinforcing the translational potential of our research (Nock et al., 2017; Chouinard‑Watkins et al., 2016, 2017; Pinçon et al., 2016; Conway et al., 2014; Vandal et al., 2014).

The recent evolution of the research program now focuses on better understanding the omega‑3 blood–brain interface, a key mechanism underlying their beneficial effects on the brain. The objective is not only to elucidate these mechanisms, but also to optimize this interface to maximize benefits, particularly in the context of aging and in APOE ε4 carriers. Special attention is also given to the broader role of brain lipids, whose metabolism is profoundly altered with age and genetic background—an area that remains underexplored and rich in fundamental and applied research questions.

The laboratory is located in the Precision Health and Translational Research Pavilion (PSPRT), a recent building within the Faculty of Medicine and Health Sciences at Université de Sherbrooke. An entire floor is dedicated to the biology of aging, offering students a modern, stimulating, and highly collaborative research environment, where complementary expertise and approaches foster innovation. PhD students benefit from a dynamic setting that promotes scientific exchange, creativity, and comprehensive training in both fundamental and translational research.

Doctorat en physiologie option neurosciences

Canada

Université de Sherbrooke

Required Skills and Technical Background

Master’s degree (or M2) in a relevant field (physiology, neurosciences, nutrition, pharmacology, or related discipline)

Ability to work with animals, including mouse handling and dissections; prior experience in animal research laboratories is considered an asset

Strong teamwork skills, critical thinking abilities, good organizational skills, and initiative

Ability to read and understand English (part of the interview will be conducted in English to assess the candidate’s proficiency)