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SWBio DTP PhD project: Ancestral functions of genes regulated by imprinting in mammals


Department of Biology & Biochemistry

About the Project

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP) https://www.swbio.ac.uk/.

The DTP offers an interdisciplinary research training programme delivered by a consortium comprising the Universities of Bath, Bristol and Exeter, Cardiff University and Rothamsted Research, alongside six regional associate partners: Marine Biological Association, Plymouth Marine Laboratory, Swansea University, UCB Pharma, University of the West of England and SETsquared Bristol.

All SWBio DTP projects will follow a structured 4-year PhD model, combining traditional project-focussed studies with a taught first year which includes directed rotation projects.

+++ Studentships are available for entry in October 2021 - please see the ’Funding Notes’ below and https://www.swbio.ac.uk/programme/eligibility/ for information on eligibility +++

SUPERVISORY TEAM:

Lead supervisor: Prof Andrew Ward, University of Bath, Department of Biology & Biochemistry, , https://researchportal.bath.ac.uk/en/persons/andrew-ward
Co-supervisors: Prof Robert Kelsh and Prof Laurence Hurst, University of Bath

OVERVIEW OF THE RESEARCH:

Around 100 mammalian genes are subject to regulation by genomic imprinting such that only one of the two parental alleles is expressed. This form of epigenetic regulation is unique to mammals and the evolution of imprinting has been hotly debated since its discovery around 30 years ago. The most widely accepted evolutionary theory for imprinting predicts a critical role for imprinted genes in regulating growth during development. However, while it is clear some imprinted genes are important regulators of growth, there are many with other functions. Much of what we know about imprinted genes comes from mouse genetic studies and relatively little is known about the functions of the analogous genes in animal species in which imprinting does not exist. For each gene with imprinted expression in mammals this project will identify orthologues in nonmammalian vertebrate and invertebrate species. By comparing gene function in different species, the aim is to test the hypothesis that imprinting first evolved to act on genes with established roles in growth regulation. Alternative hypotheses will be considered.

The PhD project will combine two main approaches to be carried out in parallel: First, through careful evaluation of the literature and genome databases, evidence of gene function in both mammalian and non-mammalian species will be gathered and evaluated. It is anticipated that functional information from studies of non-mammalian models will be scarce relative to a wealth of information for mammalian genes, particularly from mouse genetic studies. This exercise will go some way to addressing the hypothesis, and will identify a short-list of imprinted gene orthologues for functional testing in zebrafish. The second approach will involve genetic testing of gene function in zebrafish and will begin with zebrafish orthologues of Grb10, which is expressed from the maternally-inherited allele in mouse and is an important regulator of fetal growth. Mutant grb10 zebrafish strains are available and will be used to identify whether growth regulation, or other functions known from mouse genetic studies, are conserved in fish. This will involve studying morphology, histology and physiology of developing zebrafish. Additionally, the molecular phenotype will be addressed using antibody staining and mRNA in situ hybridisation to assess expression of marker genes and through the generation of an RNA-seq data set. The student will acquire both ‘wet-lab’ techniques in embryology, in vivo imaging, molecular biology, and a range of bioinformatic skills.

APPLICATIONS:

Applicants must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology.

Informal enquiries are welcomed and should be addressed to the lead supervisor.

Enquiries about the application process should be addressed to .

Formal applications should be submitted on the University of Bath’s online application form for a PhD in Biosciences: https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-DT01&code2=0005

Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section. You may apply for more than one project if you wish but you should submit a separate personal statement relevant to each one.

If you are an EU/EEA/Swiss national with settled or pre-settled status in the UK under the EU Settlement Scheme, please upload documentary evidence with your application.

More information about applying for a PhD at Bath may be found on our website https://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/.

Funding Notes

Studentships cover tuition fees at the ‘Home’ level, research/training costs and a stipend (£15,285 p.a., 2020/21 rate) for 3.5 years.

The main categories of candidates normally eligible for 'Home' fees are:
UK nationals*
Irish nationals living in the UK/Ireland
Applicants with settled or pre-settled* status in the UK under the EU Settlement Scheme
Applicants with indefinite leave to enter/remain in the UK

* must have lived in the UK/EEA/Switzerland continuously since September 2018.

If you do not qualify for ‘Home’ fees, you may be considered for an international student fee discount equivalent to the difference between ‘Home’ and ‘Overseas’ fees.

References

Garfield, A.S., Cowley, M., Smith, F.M., Moorwood, K., Stewart-Cox, J.E., Gilroy, K., Baker, S., Xia, J., Dalley, J.W., Hurst, L.D., Wilkinson, L.S., Isles, A.R. and Ward, A. (2011). Distinct physiological and behavioural functions for parental alleles of imprinted Grb10. Nature, 469, 534-538.

Cowley, M., Garfield, A.S., Madon-Simon, M., Charalambous, M., Clarkson, R.W., Smalley, M.J., Kendrick, H., Isles, A.R., Parry, A.J., Carvey, S., Oakey, R.J., Heisler, L.K., Moorwood, K., Wolf, J.B. and Ward, A. (2014). Developmental programming mediated by complementary roles of imprinted Grb10 in Mother and Pup. PLoS Biology, 12, e1001799 (13p). DOI 10.1186/s12915-014-0099-8

Madon-Simon, M., Cowley, M., Garfield, A. S., Moorwood, K. & Ward, A. (2014) Antagonistic roles in fetal development and adult physiology for the oppositely imprinted Grb10 and Dlk1 genes BMC Biology 12, 771 (22p).

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