That which does not kill us makes us stronger: Differential sensitivity to metal exposure during zebrafish embryogenesis and the impact of pre-exposur

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This studentship aims to document the epigenetic regulation of sexual differentiation and development in a fish model and how this process is perturbed by exposure to environmental stressors. The project will address the hypothesis that the (epi)genomic environment of the developing germ cells within the gonads plays a key role on the process of sex determination and subsequent differentiation of those germ cells. We also hypothesise that that some environmental stressors will perturb these processes, potentially leading to adverse outcomes for reproduction, which may be inheritable via epigenetic mechanisms in some cases. The work will focus on two ubiquitous stressors affecting fish populations worldwide, hypoxia and bisphenol A. Hypoxia is one of the most important global threats to freshwater and marine ecosystems worldwide, resulting in mass mortalities. When oxygen depletion is mild, disruption of sex differentiation in fish can to occur with potential population level consequences in affected ecosystems. Bisphenol A, a component of plastics, is present in aquatic systems globally and has been detected in over 90% of people tested. Exposure to bisphenol A causes disruption of reproduction, changes in epigenetic markers and is associated with a wide range of diseases including cardiovascular disease. These stressors are of great concern globally and there is a need to understand how they cause their effects and whether exposures can result in long term adverse effects later in life or in subsequent generations.To do this, the student will first investigate the epigenomic regulation of sexual differentiation and development in the germ cells using the zebrafish as a model. This will be achieved by isolating germ cells during the developmental windows where major sex differentiation events occur, and quantifying the transcriptome, methylome and miRNAs on those isolated cells. The student will then test how exposures to hypoxia and bisphenol A affect the development of the germ cells. Finally, the student will investigate whether the adverse effects of these stressors can be inherited via epigenetic mechanisms to subsequent generations, by conducting multigenerational studies.The research outcomes of the proposed work will provide the first global characterisation of the epigenomic factors regulating sex differentiation and development in germ cells, and the effects of globally important stressors on those processes. Given the importance of reproduction for the sustainability of fish populations, this knowledge is highly relevant to support appropriate management and regulatory decisions, and to better protect the aquatic environment.The collaboration between Cefas and the University of Exeter will bring together expertise in fish reproductive biology, epigenetics and bioinformatics that will strongly benefit all partners involved. The student will benefit from outstanding training, support and facilities on both academic and governmental research environments, covering both subject specific training and generic training in transferable skills, and will be nurtured to develop as an independent scientist able to contribute to the international research community.