About the Project
MRC Industrial Collaborative Awards in Science and Engineering (iCASE) studentship in collaboration with AstraZeneca
DNA double-strand breaks (DSBs), in which both strands of the double helix of the DNA are broken, are amongst the most toxic type of damage that cells can suffer. They can result in genome rearrangements and the loss of genetic information at the break site. The faithful repair of DSBs is therefore essential, not only for the survival of our cells but also for our growth and development, as defective repair can cause many inherited human syndromes characterised by developmental abnormalities, cancer or premature ageing. DSBs are also thought to be the main lesion causing cell death, a property that has been exploited for cancer treatment.
The two main ways used by our cells to repair DSBs are non–homologous end-joining (NHEJ), which involves ‘sticking’ or joining back together the two broken ends, and homologous recombination (HR), which involves a copy/paste type reaction utilizing information (DNA sequence) from an intact DNA template. Although our understanding of the process of DSB repair has improved in recent years, we still lack a detailed knowledge of how cells decide which pathway to use to repair DSBs, how the broken ends are processed to start HR and how cells promote and regulate this process. These are important issues in medical research and their understanding will have far reaching implications. For the many inherited human disorders caused by defective DSB repair, improving our understanding could in the future lead to the development of better management and prevention strategies. For cancer, this knowledge could mean the development of new treatments.
Recently, my lab has identified EXD2, a protein that is required for the initial key step in HR repair i.e. the resection of broken DNA ends. However, the molecular mechanism by which this novel nuclease mends broken chromosomes is unknown.
The aim of this PhD project will be to characterize the role of EXD2 in DSB repair pathway choice, genome stability maintenance and the suppression of tumourgenesis. Results from this work will help to answer fundamental questions about the role of chromosomal instability in cancer development. Moreover, molecular information gained regarding DSB repair pathway choice could pave the way for the development of new cancer treatments strategies.
This project will involve training in standard molecular and cell biology techniques, as well as cutting edge CRISPR-Cas9 genome editing, super-resolution microscopy and in vitro biochemistry. There will also be opportunities to gain experience in structural biology and the transgenic mouse model system. Students are encouraged to attend and present their work at national and international meetings.
The successful candidate will spend at least three months working alongside industry scientists at AstraZeneca’s Cambridge site.
https://d1ijoxngr27nfi.cloudfront.net/default-document-library/niedzweidz-icr-studentship-proposal-astrazeneca_wn-final-web.pdf?sfvrsn=2
Candidate profile
The successful candidate will hold or expect to obtain a B.Sc. or equivalent (First or 2:1) in Biochemistry, Molecular Biology or Genetics.
Additional eligibility criteria
This studentship is funded by the Medical Research Council. Normally to be eligible for a full award a student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship. Please see the RCUK residency requirements for further information.
How to apply
Full details about these studentship projects, and the online application form, are available on our website, at: www.icr.ac.uk/phds Applications for all projects should be made online. Please ensure that you read and follow the application instructions very carefully.
Closing date: Monday 20th November 2017
Applicants should be available for interview 29h and 30th January 2018.
Please apply via the ICR vacancies web portal https://studentapps.icr.ac.uk/
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