About the Project
The MRC has awarded the GW4 BioMed DTP additional studentships for an October 2017 start. This project is in competition with 40 that are now being advertised across the DTP.
Project Description:
The DNA damage response, highlighted recently by the Nobel Prize, plays a critical role in preserving chromatin integrity against cancer. Paradoxically, it also promotes mutagenesis to stimulate antibody diversity against immunodeficiency. This project aims to study the role of a new chromatin modifier on antibody diversification and cancer.
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 and identified a chromatin ATPase was one of the very few protein hits identified in both our screens. This ATPase is a core member of the HAT histone acetyl transferase complexes and is known to be important for genomic stability. We have now generated mice harbouring a conditional knockout allele of this ATPase and propose to test its role in immune development, antibody diversification, and tumorigenesis.
This studentship has 4 main aims with a workload divided between Exeter and Bristol. The prospective student will study the role of the new chromatin modifier in maintaining genomic stability and antibody diversification in cells and mice.
Aim1: Identify its role as a bone-fide DNA repair protein. Skills: biochemistry, computational and network analysis, Crispr/cas9 genome editing.
Aim2: Study its role in histone acetylation and effect on other histone modifications. Skills: epigenetic and DNA damage techniques.
Aim3: Identify its role in antibody diversification through somatic hypermutation and class switch recombination in cell lines and mouse spleens. Skills: animal handling, next-gen-seq, immune assays.
Aim4: Identify its potential role in lymphomagenesis through monitoring of mice for survival and tumourigenesis. Skills: animal dissection, tissue fixation, and statistical analyses.
Start date: October 2017
Academic criteria:
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 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.. 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 have achieved at least 6.5 in IELTS (and no less than 6.5 in any section) by the start of the programme.
Eligibility:
The Doctoral Training Partnership welcomes applications from both UK and EU applicants; however, as a consequence of the EU referendum result, final award decisions will depend on the outcomes of the UK/EU negotiations. If the Research Council (MRC in this instance) withdraws funding for EU students, all EU applicants will be ineligible for entry into the GW4 BioMed MRC DTP.
All EU applicants must have been ordinarily resident in the EU for at least 3 years prior to the start of their proposed programme of study. Due to funding regulations there are fewer studentships available for EU students who have not been resident in the UK for at least 3 years prior to the start of this course. By using a mixture of MRC and Cardiff University funding all studentships will be fully funded.
How to apply:
The deadline for applications is 8th June at 0930.
Applications will be via an online form and applicants will also be responsible for forwarding an academic transcript and two references to the DTP should they be shortlisted for interview.
Interviews will take place on Friday 30 June.
For an overview of the MRC GW4 BioMed programme, please see website www.gw4biomed.ac.uk
For project related queries, please contact Dr Richard Chahwan.
Funding Notes
Studentships are funded through the GW4 BioMed MRC Doctoral Training Partnership. Projects are fully funded for 3.5 years (or up to 7 years part-time). and consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,553 for 2017/18, updated each year).
Additional funding, dependent on the project, is available over the course of the programme (dependent of the research requirements). This covers costs such as research consumables, training, conferences and travel.
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