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  NERC iCASE studentship: Epigenomic regulation of germ cell development in fish and its modulation by environmental stressors


   College of Life and Environmental Sciences

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  Dr E Santos, Prof J MIll, Dr Emma Dempster, Dr R van Aerle  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

The University of Exeter, in partnership with the Centre for Environment, Fisheries and Aquaculture Science (Cefas), is inviting applications for a NERC Industrial CASE-funded PhD studentship to commence in September 2017 (or as soon as possible thereafter).

Project Description:

This studentship aims to document the epigenetic regulation of sexual differentiation and development in zebrafish 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 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 aquatic ecosystems, resulting in mass mortalities. When oxygen depletion is mild, disruption of sex differentiation in fish can 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 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.

Firstly, the student will investigate the epigenomic regulation of sexual differentiation and development in the germ cells using the zebrafish. 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, by conducting multigenerational studies.

The research outcomes of the proposed work will provide the first characterisation of the epigenomic factors regulating sex differentiation and development in germ cells, and the effects of important stressors on those processes. This knowledge is highly relevant to support appropriate management of water systems and regulatory decisions to better protect the aquatic environment.

The collaboration between the Universities of Exeter and Cardiff and Cefas will bring together expertise in fish reproductive biology, toxicology, epigenetics and bioinformatics that will strongly benefit all partners. The student will benefit from outstanding training, support and facilities in both academic and governmental research environments, covering subject specificand generic training in transferable skills, and will be nurtured to develop as an independent scientist.

See http://www.exeter.ac.uk/studying/funding/award/?id=2251 for full details and how to apply.


Funding Notes

The University of Exeter, in partnership with the Centre for Environment, Fisheries and Aquaculture Science (Cefas), is inviting applications for a NERC Industrial CASE-funded PhD studentship to commence in September 2017 (or as soon as possible thereafter).

The studentships will provide funding for a stipend which is currently £14,296 per annum for 2016-2017, research costs and UK/EU tuition fees at Research Council UK rates for 42 months (3.5 years) for full-time students, pro rata for part-time students.

References

1. L. V. Laing et al., Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio). Epigenetics. 11, 526, 538 (2016).

2. J. A. Fitzgerald et al., Hypoxia suppressed copper toxicity during early development in zebrafish embryos in a process mediated by the activation of the HIF signaling pathway. Environ. Sci. Technol. 50, 4502, 4512 (2016).

3. E. Hannon et al., Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. Nat. Neurosci. 19, 1–9 (2015).

4. W. Xie et al., Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell. 148, 816, 831 (2012).

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