ELCHA Investigators awarded Spring 2023 CIHR Project Grants

Congratulations to the the Investigators of the Edwin S.H. Leong Centre for Healthy Aging who won Project Grants in the most recent CIHR competition! Read below to see how these funds will be used to support health research.

PI: Dr. Ramon Klein Geltink ($983,026)

Title: Glucose restriction-mediated changes to mitochondria as a driver of anti-tumour CD8+ T cell function.

Summary: CD8+ T cells are part of the immune system and play a key role in eliminating cancerous cells in our body. CD8+ T cells are activated when they encounter tumour-expressed target proteins through their unique receptor. Each cell expresses a receptor that is unique for an individual target protein. This activation leads to differentiation and production of effector molecules, which is strongly linked to the activity of metabolic pathways that break down nutrients to produce both energy and cellular building blocks. The ability of CD8+ T cells to produce crucial effector molecules that are used to rid the body of cancerous cells is dependent on the metabolic breakdown of sugars (glucose), also referred to as glycolysis. In previously published work, the Klein Geltink Lab showed that limiting the breakdown of glucose temporarily drives adaptations in CD8+ T cells that ultimately improved anti-cancer function of these cells. Although they could readily show differences in energy generating metabolic pathway activities, we do not know how CD8+ T cell function is regulated by these adaptations. This new funding will allow Dr. Klein Geltink’s Lab to uncover the mechanisms that impact CD8 T cell activity against cancer, by investigating the pathways that sense glucose availability, metabolic pathway activity, and T cell activation through their target-specific receptor. This work will illuminate new targets that could be used to bolster CD8 T cell activity against cancer, and could provide insight into the lab-based generation of superior CD8 T cells for the treatment of cancer.

PI: Dr. Thibault Mayor ($1,005,976)

Title: Elucidation of the client repertoires and functions of the two related DNAJB6 and B8 co-chaperones

Summary: Proteins typically need to adopt a specific three-dimensional conformation to gain functionality. Failure to reach or maintain the proper conformation is deleterious, as proteins then have the tendency to aggregate. Therefore, a large number of different protein chaperones have evolved, nearly 200 in humans, in order to support protein folding. However, the capacity to support protein folding diminishes upon aging and under stress conditions, which partially explains why protein deposition is often observed in neurodegenerative diseases such as in Huntington’s disease. Despite major efforts, there are still no cures for these diseases, partially due to our limited knowledge of how proteins are folded in the cells. Interestingly, several chaperones can reduce the disease burden and protein aggregation when over-expressed, like DNAJB6 and DNAJB8 that are normally only expressed in testis. Nonetheless, the normal functions of these two related co-chaperones are not well understood. With this new funding, the Mayor lab will further develop a proteomic approach to better characterize which clients interact with each chaperone, and determine which elements on these chaperones dictate client specificity. Their work will help elucidate the function of conserved chaperones that have potential major roles in protein homeostasis, neurodegenerative diseases and aging.

PI: Dr. Rachel Murphy ($1,732,726)

Title: HEALthy Eating and Supportive Environments (HEAL); a Pan-Canadian study

Summary: Most Canadians do not consume diets that align with health recommendations. As a result, poor diet is among the leading causes of chronic diseases like cancer, heart disease, and diabetes in Canada. The environment where people live, work and play is increasingly recognized as an important factor shaping dietary intake, and is potentially modifiable. However, in order to drive meaningful improvements in the dietary intake of Canadians, we need to gain a better understanding of how environments support healthy eating. The aims of this project are to 1) describe how dietary intake is linked with aspects of the food environment like how accessible healthy foods are within communities, provinces and across Canada, 2) examine how links between dietary intake and the food environment group with other environmental factors like how walkable a neighbourhood is and factors known to influence chronic disease risk such as physical activity, income and education. To accomplish these aims, the team will collect data on diet, physical activity and other health factors with user-friendly online tools in a large study of men and women across 8 provinces; the Canadian Partnership for Tomorrow Project (CanPath) and connect with NutriQuébec, an ongoing cohort collecting similar data. CanPath and NutriQuébec, are linked to nation-wide environment data including measures of the food, social and built environments, creating a rich data source to explore our novel research questions. This study will contribute critical evidence that may help support approaches to improve the dietary intake of Canadians.