PhD Studentship: Targeting chromatin defects in cancer

PhD Studentship Genome Stability University of Sussex Funding for: UK Students Funding amount: Home (UK) tuition fees and stipend at standard UKRI rates. A PhD studentship (3.5 years) is available from September 2024 under the supervision of Prof. Timothy Humphrey, Genome Damage & Stability Centre (GDSC), School of Life Sciences. Deadline: 28th February 2024 Project Title Targeting chromatin defects in cancer The project All DNA transactions, including DNA replication, DNA repair and transcription occur within the context of chromatin. Accordingly, mutations affecting chromatin can result in wide-ranging pleiotropic effects, which can lead to genetic disease, including cancer. Consistent with this, gain or loss of function mutations in histone variants, chromatin remodellers, and histone modifiers are frequently observed in cancers, thereby representing actionable vulnerabilities. The aim of this project is to target particular chromatin defects to treat cancer. This will be achieved through initially confirming the suitability of particular mutations as cancer targets. Secondly, synthetic lethal interactions with these mutations will be identified, using model systems, including yeast and human cell lines.  Lastly, we will exploit these synthetic lethal interactions obtained to target cancers carrying particular chromatin mutations of interest.  Using this approach, we have contributed to clinical trials targeting SETD2-deficient cancers (Pfister et al., Cancer Cell 2015); P53-KRAS colorectal cancers (Seligmann et al., J Clin Oncol 2021) with others in progress. Techniques will include yeast and mammalian genetics, CRISPR, molecular biology, biochemistry and immunohistochemistry. The team You will work within the Chromatin Integrity Group led by Prof. Timothy Humphrey, in the Genome Damage and Stability Centre, which is a Centre of Excellence at the University of Sussex, Brighton. We benefit from strong interactions with discovery and clinical researchers, the Sussex Drug Discovery Centre, Life Sciences and pharmaceutical companies. Informal enquiries about the project can be made to Prof Timothy Humphrey at timothy.humphrey@sussex.ac.uk How to apply: Please submit a formal application using the online admissions portal attaching a CV, degree transcripts and certificates, personal statement, and two academic referees. A research proposal is not required. On the application system select Programme of Study – PhD Genome Stability. Please state the project title under funding obtained and the supervisor’s name where required. Candidates should have or expect to obtain a minimum 2:1 undergraduate degree. An MSc degree will be advantageous. Your qualification should be in Genome Stability or a related subject area. You may also be considered for the position if you have other professional qualifications or experience of equivalent standing. Candidates for whom English is not their first language will require an IELTS score of 6.5 overall, with not less than 6.0 in any section - English language requirements Applications are particularly welcomed from candidates with protected characteristics – e.g., from Black and other ethnic minorities – who are under-represented in postgraduate research at our institution. For enquiries about the application process, please email Emma Chorley: lifesci-rec@sussex.ac.uk