Dynamic structures of protein-DNA organization in irradiated and re-irradiated cancer cells

Research Overview:<br /> <br /> Radiotherapy is a fundamental component of modern cancer treatment. It employs ionizing radiation to target and destroy cancer cells by inducing lethal DNA damage and causing structural changes within the nucleus. Despite its widespread application, the specific structural alterations within the nucleus in response to irradiation remain largely unclear. Even less is known about the effects of repeat radiotherapy, commonly referred to as re-irradiation, at cellular and chromatin levels. As re-irradiation is increasingly being considered for recurrent tumours, understanding its impact on chromatin dynamics is essential for enhancing radiation sensitivity in cancer cells while minimizing damage to healthy tissues. Ultimately, this knowledge aims to optimize treatment strategies and improve patient outcomes.<br /> <br /> Project Training and Support:<br /> <br /> This PhD project presents an exciting opportunity to investigate the nanoscale structural changes in chromatin within cancer cells following irradiation and re-irradiation. The student will receive structured and comprehensive training in our groups and facilities specificizing cutting-edge cell imaging and cellular structural biology methods, including cryo-electron microscopy/tomography (cryo-EM/ET), focused ion beam (FIB) milling with scanning electron microscopy (SEM) and correlative light and electron microscopy (CLEM). These techniques will be used to analyse clinical cancer samples subjected to various radiation doses and exposure conditions.<br /> <br /> This studentship serves as a crucial link between discovery research and clinical practice. The PhD student will be supervised by a diverse and experienced supervisory team with expertise in discovery biology from the Faculty of Biological Sciences (Dr Qian Wu, Prof Richard Bayliss) and clinical research from the Faculty of Medicine and Health (Prof Adel Samson and Dr Louise Murray). The student will be part of the Leeds Cancer Research UK (CRUK) Radiotherapy Centre of Excellence (RadNet Leeds) and engage with vibrant communities from the Astbury Centre and the newly established Cheney Biomedical Accelerator. <br /> <br /> For more information about this project, please get in touch with Dr. Qian Wu (q.n.wu@leeds.ac.uk)

<p>Recent research publications from supervisor’s groups:</p> <p><br /> 1) Ryder, E.L., Nasir, N., Durgan, A.E., Jenkyn-Bedford, M., Tye, S., Zhang, X. and Wu, Q., 2024. Structural mechanisms of SLF1 interactions with Histone H4 and RAD18 at the stalled replication fork. Nucleic Acids Research, 52(20), pp.12405-12421. <br /> 2) Sampson J, Ju HM, Zhang N, Yeoh S, Choi J, Bayliss R, Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer. Cell Death Dis. 2024 Dec 18;15(12):912. doi: 10.1038/s41419-024-07272-7.<br /> 3) E. J. West, A. Sadoun, K. Bendjama, P. Erbs, C. Smolenschi, P. A. Cassier, T. De Baere, S. Sainte-Croix, M. Brandely, A. A. Melcher, F. Ismail, K. J. Scott, A. Bennett, E. Banks, E. Gasior, S. Kent, M. Kurzawa, C. Hammond, J. V Patel, F. J. Collinson, C. Twelves, D. A. Anthoney, D. Swinson, A. Samson. A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer. Clinical Cancer Research, 2025.<br /> 4) Murray LJ, Appelt AL, Ajithkumar T, Bedford JL, Burnet NG, Lalondrelle S, Manolopoulos S, O'Cathail SM, Robinson M, Short SC, Slevin F, Thomson DJ. Re-irradiation: From Cell Lines to Patients, Filling the (Science) Gap in the Market. Clin Oncol (R Coll Radiol). 2023 May;35(5):318-322. <br />  </p>

<p>Formal applications for research degree study should be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University's website</a>. Please state clearly in the research information section that the research degree you wish to be considered for is Dynamic structures of protein-DNA organization in irradiated and re-irradiated cancer cells as well as <a href="https://biologicalsciences.leeds.ac.uk/biological-sciences/staff/1136/dr-qian-wu">Dr Qian Wu | Faculty of Biological Sciences | University of Leeds</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University'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>We are offering 1 full-time PhD scholarship in the Faculty of Biological Sciences for one UK candidate, covering a maintenance grant matching UKRI maintenance stipend for 4 years (currently £20,780 in 2025/26) and UK tuition fees in full, subject to satisfactory progress. The award will be made for one year in the first instance and renewable for a further period of up to three years, subject to satisfactory academic progress. </p> <p>Applicants must live within a reasonable distance of the University of Leeds whilst in receipt of this scholarship and will be expected to join in with our thriving research community. </p> <p> </p>

<p>For further information please contact the Graduate School Office<br /> e: <a href="mailto:EMAIL@leeds.ac.uk">fbsgrad@leeds.ac.uk</a></p>