Regulation and function of the stress response in fish

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The stress response plays an essential role in maintaining the optimal body equilibrium in the face of adverse forces, but we know relatively little about the intricate and interconnected neuroendocrine, cellular, and molecular pathways that regulate this adaptive physiological response. Therefore, the long-term objective of my research program is to understand the mechanisms responsible for context-specific stress responses. Key among the effectors of the stress response is corticotropin-releasing factor (CRF) and cortisol, the principle central regulator and the end-product of the neuroendocrine stress axis, respectively. As such, identifying novel actions of CRF and cortisol, and determining their physiological relevance for maintaining homeostasis are also ongoing objectives of my research program. Our recent research advances on three fronts form the basis of this proposal. First, we identified that CRF has cytoprotective effects against environmental stressors in fish, including neuroprotective actions, and now seek to identify the specific mechanisms by which CRF prevents neurodegeneration and promote neuro-regeneration. Second, we determined that components of the CRF system are expressed in the gills and intestine of fish and showed that these are responsive to changes in salinity, prompting further research into the osmoregulatory functions of the CRF system. Lastly, we discovered that chronic exposure to environmental stressors increases the maternal-to-offspring transfer of heat shock proteins, mediators of the cellular stress response, and a reduction in egg cortisol content, the functional consequences of which are unknown. Therefore, the proposed research will address three short-term objectives: (1) determine the mechanisms by which the retinal CRF system is cytoprotective; (2) identify the contributions of the gill and intestinal CRF systems to osmoregulatory functions; and (3) determine how exposure to maternal environmental stressors impacts offspring stress tolerance. To address these objectives, we will use a comprehensive suite of techniques ranging from the whole animal to the molecular levels and select research models ideally suited for the question at hand. The funding requested will allow me to train at least 3 PhD, 3 MSc, and 10 BSc students, who will obtain advance and diverse technical skills that are invaluable for diverse scientific careers. Our research is expected to have a broad impact on our fundamental understanding of how fish have evolved solutions to handle environmental stressors. Specifically, our research will impact our understanding of the mechanisms involved in maintaining retinal integrity, extend our understanding of the evolutionary-conserved functions of the CRF system by providing the first mechanistic insight into the osmoregulatory functions of CRF, and offer fundamental insights into the mechanisms by which stressors encountered in the parental generation program progeny stress tolerance.