The accurate repair of double strand breaks (DSB) in DNA is key for cell survival and prevention of mutations or chromosomal translocations that might lead to cancer. When a DSB occurs this leads to transcription at the site of the DSB and production of damage induced long non-coding RNAs (dilncRNAs) which are processed with DROSHA and DICER to generate DNA damage response RNAs (DDRNAs). The DDRNAs are subsequently involved in the recruitment of other DNA repair proteins that fix the DSB (1). We have recently identified a key factor involved in driving the transcription of dilncRNAs, which is frequently mutated in cancer cells. In this project you will use state of the art CRISPR engineered human cells which have a conditional knockout for the newly identified DNA repair factor. You will study its role in transcription of DDRNAs and recruitment of both RNA processing factors and DNA repair factors to sites of DSB. The impact of mutations identified in cancer cells will also be investigated. The project will make extensive use of next generation DNA sequencing technologies coupled with methods such as CHIPseq and confocal microscopy to study the production and processing of DDRNAs and their role in the recruitment of other DNA repair factors. You will join a large well funded laboratory working on a range of different human RNA binding proteins and their roles in human disease.
The project is jointly supervised by Prof. Stuart Wilson (http://genome.sheffield.ac.uk/people/professor-stuart-wilson/) and Prof Sherif El-Khamisy (https://www.sheffield.ac.uk/biosciences/people/academic-staff/sherif-el-khamisy) who will provide a broad training in modern molecular and cell biology relevant to the DNA damage response and cancer.
For recent outputs from our laboratories see https://doi.org/10.1038/s41467-021-25459-w and https://doi.org/10.1016/j.molcel.2019.04.034 .
For informal enquiries please contact Prof Stuart Wilson : [Email Address Removed]
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme and how to apply can be found on our website:
http://www.dimen.org.uk/how-to-apply/application-overview
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