Metabolic Analyzer for the study of live cells and tissue explants

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In this proposal the funds requested will support an Agilent Seahorse Metabolic Analyzer XFe24 instrument, which uses live cells or tissue explants in a 24-well plate format to measure oxygen consumption, mitochondrial stress and extracellular acidification rates. It allows the study of cell or tissue specific responses to substrates, inhibitors and other peptides like hormones in real-time. The purchase of this instrument will greatly support the research programs of Drs. Beaudry, Comelli, Bazinet, O'Connor, and Anderson, five investigators in the Department of Nutritional Sciences at the University of Toronto and Dr. Sung, an investigator at the SickKids Research Institute. Together these researchers have mutual interests in understanding fundamental mechanisms by which nutrient and environmental factors affect physiology. The above mentioned, all have active NSERC DGs for which the requested equipment will be applied. Dr. Jacqueline Beaudry is a newly appointed (July 2020) Assistant Tenure-track Professor and principle applicant on this proposal. The overall objective of her research program is to understand how fat is influenced by glucocorticoids (GCs) or stress hormones. Her interests are focused on the essential mechanisms involved in GC signaling within the white (used for fat storage) and brown (used for dissipation of energy) fat tissue and how it regulates body weight. This instrument will allow intricate investigation into the function of how GC pathways affect mitochondrial function within fat tissue. This will lead to a better understanding of how chronic and high levels of GCs can increase fat tissue growth, which impacts overall body weight. Importantly, this machine will be used by all HQP supervised under the listed co-applicants, reinstating the desire and need for this instrument as a shared part of the Beaudry laboratory. Dr. Comelli will use the equipment to study explants and cell lines of the intestine and how they interact with the gut microbiota and its metabolites. Dr. Bazinet will investigate fatty acid substrates and how they interact with fat tissue. Dr. O'Connor will study the impact of folic acid and how it affects the availability and absorption of colonic folate. Dr. Anderson will focus his investigations in gut-brain signals involved in food intake and glucose regulation in response to amino and/or fatty acid receptor antagonists or agonists. Dr. Sung will focus his experiments on fat tissue plasticity and will investigate the adaptations to metabolic challenges that induce browning of white fat tissue. Procurement of this equipment will provide the first accessible Seahorse instrument to St. George Campus, at the University of Toronto. It will position Dr. Beaudry and co-applicants' laboratories for success in creating high-level research and impactful HQP training, ensuring the University of Toronto maintains its position as a leading research institute in Canada and remains competitive globally.