About the award
DNA repair, highlighted in this year’s Nobel Prize, plays a critical role in preserving genomic integrity against cancer. Paradoxically, it also promotes mutagenesis of immunoglobulins to stimulate immune diversity. Failure to do so could lead to cancer or immunodeficiency. This project aims to study the role of a new chromatin modifier on antibody diversification and tumorigenesis.
Research theme: Infection, Immunity & Repair
Location: Biosciences, College of Life and Environmental Sciences, Streatham campus, University of Exeter
Dr. Richard Chahwan, University of Exeter
Dr. Abderrahmane Kaidi, University of Bristol
Dr. Nicholas Harmer, University of Exeter
Full Project Description:
Cancer is one of the major public health problems in the UK and across the world. The likelihood of an individual getting cancer is greatly increased by genetic conditions involving mutations in DNA repair proteins, which typically safeguards genomic stability. Ironically, DNA repair can also promote mutagenesis at the immunoglobulin locus of B cells to stimulate antibody immune diversification. Failure to efficiently propagate these two conflicting processes could lead to tumorigenesis and immunodeficiencies, respectively.
We have recently conducted two independent genome-wide screens: 1) a proteomic screen to identify novel DNA mismatch repair proteins (with Edelmann lab in NY); and an 2) shRNA screen to identify novel proteins involved in antibody diversification (with Martin lab in Toronto). RuvBL2 ATPase/helicase was one of the very few protein hits identified in both our screens. RuvBL2 is a core member of the TIP60 histone acetyl transferase complex and is known to be important for genomic stability. Because the loss of RuvBL2 is incompatible with life (our unpublished data), we have now generated mice harbouring a conditional knockout allele of RuvBL2 and propose to test its role in immune development, antibody diversification, and tumorigenesis.
This studentship has 4 main aims with a workload divided between Exete, Bristol, and possibly New York.
The ‘MRC GW4 BioMed DTP’ brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of medical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinarity and 'team science'. Many of the PhD projects supported by the DTP will be co-supervised across at least two of the partner universities, allowing students to join existing and emerging research partnerships.
The ‘MRC GW4 BioMed DTP’ is awarding 18 studentships per annum, aligned with the themes of Infection, Immunity and Repair; Neuroscience and Mental Health; and Population Health. The DTP also places a strong emphasis on cross-cutting skills priorities (quantitative skills, interdisciplinary skills and in vivo skills), and may advertise projects outside these themes. The DTP welcomes students from non-medical backgrounds and can fund additional training to assist discipline conversion. Most studentships will be 3.5 years full time or up to 7 years part-time, and can be longer where additional training is undertaken.
This studentship is funded through the MRC GW4 BioMed Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,057 p.a. for 2015/16, updated each year).
The research project listed above is in competition with 46 other projects available across the GW4 BioMed Doctoral Training Partnership. The 18 projects which receive the best applicants will be awarded the funding.
Additional funding, dependent on the project is available over the course of the programme (dependent of the research requirements). This will covers costs such as research consumables, training, conferences and travel. Additional funds are available for high-cost training/research.
Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students who can satisfy UK residency requirements. To be eligible for the full award, EU Nationals must have been in the UK for at least 3 years prior to the start of the course for which they are seeking funding, including for the purposes of full-time education. A small number of awards may also be made available to EU Nationals who do not meet the above residency requirement, provided that they have been ordinarily resident in the EU for at least 3 years prior to the start of their proposed programme of study.
Academic criteria: Applicants for a studentship 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 medical sciences. The DTP welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences, and can fund additional training, including Masters to assist discipline conversion. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant non-academic experience.
English requirements: If English is not your first language you will need to meet the English language requirement of at least 6.5 in IELTS (alternative tests may be acceptable, see http://www.exeter.ac.uk/postgraduate/apply/english/).