Grant: Research Tools and Instruments

Stress has major physiological effects in all vertebrates. In particular, early-life stress can “program” physiology, with enduring consequences that last into adulthood. Glucocorticoids are steroid hormones that mediate the stress response. These hormones are secreted from the adrenal glands and reach their numerous target cells via the blood. In addition, exciting new research shows that glucocorticoids are locally synthesized and metabolized within the brain, lymphoid organs, and reproductive tissues.******My NSERC Discovery Grant and Discovery Accelerator Supplement focus on the local synthesis of glucocorticoids in the brain and lymphoid organs during early development. In particular, I will examine the regulation by environmental stressors, mechanisms of action, and long-lasting effects of local glucocorticoids. Prof. Collier's Discovery Grant focuses on UDP-glucuronosyltransferase enzymes. These enzymes reduce local levels of glucocorticoids via metabolism and play critical roles in development and reproduction. Both of our projects integrate multiple techniques, including molecular biology, bioinformatics, and liquid chromatography tandem mass spectrometry (LC-MS/MS).******For both projects, it is critical to measure local levels of glucocorticoids in microdissected tissue: brain and lymphoid organs (Soma) or reproductive tissues (Collier). This key task faces technical challenges, in particular the need for specific and ultrasensitive assays. With regard to specificity, mass spectrometry is the gold standard, and our labs are pioneers in developing mass spectrometry assays for steroids. With regard to sensitivity, the steroid assays in our labs are among the most sensitive in the world. However, steroids do not ionize readily, which limits the ability to measure low amounts of steroids (. The microLC can be integrated seamlessly with our existing state-of-the-art mass spectrometers. Failure to obtain the requested equipment will greatly delay our studies on local glucocorticoids.******This equipment is urgently needed to understand how stress “gets under the skin” to affect physiology. In addition, the advances in mass spectrometry will accelerate endocrine research worldwide and equip our HQP with cutting-edge technical skills that are in high demand in academia and industry. The fundamental knowledge gained from this project will impact a variety of disciplines, including endocrinology, enzymology, physiology, neuroscience, immunology, and analytical chemistry.