Metabolic Analyzer for the study of live cells and tissue explants

在这项提案中，申请的资金将支持安捷伦海马代谢分析仪XFe24仪器，该仪器使用24孔板格式的活细胞或组织外植体来测量氧气消耗、线粒体应激和细胞外酸化率。它允许实时研究细胞或组织对底物、抑制剂和其他多肽(如激素)的特定反应。 购买这台仪器将极大地支持多伦多大学营养科学系的五名研究人员Beaudry、Comelli、Baznet、O‘Connor和Anderson博士以及SickKids研究所研究员Sung博士的研究计划。这些研究人员共同感兴趣的是，了解营养和环境因素影响生理的基本机制。上述人员都有现役的NSERC DG，将为其申请所需的设备。 Jacqueline Beaudry博士是新任命的(2020年7月)终身教职跟踪助理教授和这项提案的主要申请人。她研究计划的总体目标是了解糖皮质激素(GC)或应激激素是如何影响脂肪的。她的兴趣主要集中在白色(用来储存脂肪)和棕色(用来消耗能量)脂肪组织中GC信号的基本机制，以及它如何调节体重。该仪器将允许对GC通路如何影响脂肪组织内线粒体功能的功能进行复杂的研究。这将有助于更好地理解长期和高水平的GCs如何增加脂肪组织生长，从而影响整体体重。 重要的是，这台机器将由列出的共同申请者监督的所有HQP使用，恢复了对这台仪器作为博德里实验室共享部分的渴望和需求。科梅利博士将使用该设备研究肠道的外植体和细胞系，以及它们如何与肠道微生物区系及其代谢物相互作用。巴齐内博士将研究脂肪酸底物以及它们如何与脂肪组织相互作用。奥康纳博士将研究叶酸的影响，以及它如何影响结肠叶酸的可利用性和吸收。安德森博士将重点研究与食物摄取和葡萄糖调节有关的肠脑信号，以应对氨基和/或脂肪酸受体拮抗剂或激动剂。宋博士将专注于脂肪组织的可塑性实验，并将研究其对导致白色脂肪组织褐变的代谢挑战的适应性。 购买这种设备将为多伦多大学的圣乔治校区提供第一台可获得的海马乐器。它将使博德里博士和共同申请者的实验室在创造高水平的研究和有效的HQP培训方面取得成功，确保多伦多大学保持其作为加拿大领先研究机构的地位，并保持全球竞争力。

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.