Cortisol stress axis development and function in fish

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My research program seeks to discover novel cellular signals and transduction pathways modulated by the stress steroid cortisol, and to advance our fundamental knowledge of how these responses are integrated at the whole animal level to drive function. My short-term objective for this 5-year program, is to address the role played by maternal cortisol in programming the development of offspring stress axis function. The overriding hypothesis is that maternal stress and the associated increase in cortisol deposition to the embryo will decrease cortisol clearance mechanisms prior to hatch and will lead to dysfunctions to offspring corticosteroid stress axis performance. Three specific concepts are being addressed: i) Is maternally transferred cortisol absolutely essential for zebrafish (Danio rerio) development and what are the underlying mechanisms of action? ii) At what level of cortisol does this maternal contribution switch from being essential to unhealthy and what is the mode of action? iii) Is corticosteroid signaling essential for early development and what is the mode of action? The scientific approach using zebrafish and rainbow trout (Oncorhynchus mykiss) will involve studies at multiple levels of organization, including whole animal, tissue and in vitro cell preparations, gene knockdown studies and embryo transcriptome profiling, to elucidate the molecular mechanisms involved in cortisol action during development. The proposed studies are transformative and will chart a new course in stress research with the focus on how offspring phenotype is dictated by parental stress and abnormal cortisol deposition in eggs. This fundamental research has potential applications in environmental and aquaculture sectors where stress is a major factor affecting phenotype. The discovery of novel corticosteroid-related targets involved in developmental programming may also assist in our understanding of fetal stress-related disorders and birth defects in mammals. This program is interdisciplinary and will train at least nine graduate students, three PDFs and several undergraduate students in cutting edge research involving physiology, molecular biology and developmental biology.