Disrupted SUMO signalling in epithelial cancers, implications for genome stability and response to therapy.

The School of Molecular and Cellular Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.<br /> <br /> Conjugating SUMOs1-3 (Small Ubiquitin-like Modifiers) to proteins has important roles in protein localisation, stability, and activity. SUMO signalling is implicated in a wide range of cellular processes. A small family of SUMO proteases (SENPs) remove SUMOs from proteins. When the balance between SUMOylation and deSUMOylation is disrupted, many cellular pathways can be affected. We have evidence that this occurs in several types of disease, including cancer.

<p>Some cancers of the lung, head/neck, endometrium, and ovaries have a chromosomal amplification that includes SENP genes. This amplified region also includes important DNA repair enzymes. This project will look at the effects of the chromosomal amplification 3q, on the ability of cells to repair DNA damage caused by chemotherapy. The project will assess the contribution that 3q disrupted SUMO signalling has to chemotherapy response, and whether this can be exploited to treat cancer.</p> <p>This project will use cutting edge molecular and cell biology techniques to interrogate DNA damage and SUMO signalling in cancers with and without chromosome 3q amplification. The lab is based in a newly renovated space co-located with ~12 molecular and cell biology research groups. The student will benefit from an excellent work environment supported by state-of-the-art research infrastructure within the faculty.</p> <p>References:</p> <ul> <li>The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms. Alexander J Garvin, Alexandra K Walker, Ruth M Densham, Anoop Singh Chauhan, Helen R Stone, Hannah L Mackay, Mohammed Jamshad, Katarzyna Starowicz, Manuel Daza-Martin, George E Ronson, Alexander J Lanz, James F Beesley, Joanna R Morris. Genes Dev. 2019 Mar 1;33(5-6):333-347. doi: 10.1101/gad.321125.118.</li> <li>The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair. Alexander J Garvin, Ruth M Densham, Sarah A Blair-Reid, Kenny M Pratt, Helen R Stone, Daniel Weekes, Kirsty J Lawrence, Joanna R Morris. EMBO Rep. 2013 Nov;14(11):975-83. doi: 10.1038/embor.2013.141.</li> <li>SUMO, a small, but powerful, regulator of double-strand break repair. Alexander J Garvin, Joanna R Morris. Philos Trans R Soc Lond B Biol Sci. 2017 Oct 5;372(1731):20160281.</li> </ul>

<p>To apply for this project opportunity applicants should complete an <a href="https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply">online application form</a> and attach the following documentation to support their application.&nbsp;</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks</li> <li>Evidence that you meet the University&#39;s minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Biological Sciences as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<p>This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.&nbsp;</p>

<p>For information about the application process please contact the Faculty Admissions Team:</p> <p>e: <a href="mailto:fbsgrad@leeds.ac.uk">fbsgrad@leeds.ac.uk</a></p>