PhD Studentship: Identification and Characterisation of Novel DNA Damage Response Factors (BBSRC Funded)

University of Exeter - Medical School

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.

Academic Supervisors:

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

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 signalling cascade.

The proposed project aims to elucidate and focus on the contribution of epigenetic marks – including histone modifiers and non-coding RNA signalling – 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, next-generation sequencing, meta-analysis of 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 hypermutation 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.

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South West England