Identification and Characterisation of Novel DNA Damage Response Factors - Medicine, PhD (BBSRC SWBio DTP Funded)

The South West Biosciences Doctoral Training Partnership (SWBio DTP) is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence. The partnership has a strong track record in advancing knowledge through high quality research and teaching in partnership with industry and government.

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP). Up to 4 fully-funded studentships are being offered to start in September 2018 at the University of Exeter.

Supervisory team:

Main supervisor: Dr Benjamin Housden
Co-supervisor: Dr Richard Chahwan
Collaborator: Prof Matthew Scharff
Collaborator: Dr Thomas MacCarthy

Location: University of Exeter, Streatham Campus, Exeter

Project description:

Humans and other mammals are required to strike a fine balance between maintaining DNA integrity and mutating their immunoglobulin gene to generate immune diversity. Paradoxically, both processes require the involvement of the DNA damage response (DDR), which safeguards our bodies from tumorigenesis and immunodeficiency. DNA repair factors in conjunction with chromatin modifications have been established to play an important role in DDR. We and others have recently shown that histone ubiquitination is important for both the maintenance of genomic stability and the mitigation of the Riddle Syndrome immunodeficiency – harbouring a defective RNF168 ubiquitin ligase protein. We now intend to conducted further genome-wide screening analyses to identify other novel DNA repair factors and map their role within the broader DDR signaling cascade.

The proposed project aims to elucidate and focus on the contribution of epigenetic marks – including histone modifiers and non-coding RNA signaling – for the maintenance of genomic stability, promotion of antibody diversity, and protection against premature ageing. Successful PhD candidates will be conducting this work in a vibrant research environment at the Living Systems Institute – University of Exeter, with the potential to spend some time in New York and/or Boston. The proposed PhD project will rely on various computational, molecular, and cellular techniques that have been optimized in the lab. These include: high-throughput screening, nextgeneration sequencing, meta-analysis of 4 / 13 ENCODE, STRING and IMMGEN databases, culture and genetic manipulation of Drosophila and mammalian cells, various methods to assess the efficacy of the DNA damage response, and various methods to measure the efficacy of the immune response including somatic hyermutation and class switch recombination. The project will also rely on our novel technologies for genetic manipulation of Drosophila and mammalian cells using CRISPR and novel genome-wide screening tools that we have recently established.

Entry requirements:

Applicants should 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. Applicants with a Lower Second Class degree will be considered if they also have Masters degree or have significant relevant non-academic experience.

In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification or experience is required.

If English is not your first language you will need to have achieved at least 6.5 in IELTS and no less than 6.5 in any section by the start of the project. Alternative tests may be acceptable, please see http://www.bristol.ac.uk/study/language-requirements/profile-c/.

Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award but no stipend. Applicants who are classed as International for tuition fee purposes are not eligible for funding. Further information about eligibility can be found in the following document: http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/