(MCRC Non-Clinical) Exploiting Chromosomal Instability Across the Ovarian–Endometrial Axis: Models, Mechanisms and Therapeutic Targeting

About the project

About the Project The most aggressive ovarian and endometrial cancers converge on a common phenotype: extensive chromosomal instability (CIN) – ongoing chromosomal changes that generate karyotypic heterogeneity within a tumour, linked to poor patient outcomes. This project asks whether this instability creates shared vulnerabilities we can exploit to find new treatments for patients who currently have few options. This project will address three main areas: Many cancer cell lines were classified before current molecular taxonomies existed, and endometrial cancer lines lack the histotype benchmarking already established for ovarian cancer. Using transcriptomics and machine learning, you will build the first harmonised classification of ovarian and endometrial cancer cell lines, revealing therapeutic targets hiding in plain sight. You will generate new endometrial cancer models, using modern culture conditions designed to preserve tumour diversity, something older methods often failed to capture. You will analyse these models alongside ovarian cancer models from our Living Ovarian Biobank, challenging both with existing and emerging drugs and using long-read sequencing to map the genomic changes underlying chromosomal instability, linking mechanism directly to treatment response. Finally, you will address a fundamental open question: where do these cancers actually originate? Using DNA methylation-based lineage tracing, you will compare normal and cancerous tissue from the ovary, fallopian tube and endometrium to trace each tumour's cell of origin and test whether it shapes biology and treatment response. Throughout, you will work within an interdisciplinary team of clinicians and scientists, gaining a thorough grounding in wet-lab and bioinformatic techniques spanning cell biology, translational oncology and genomics. You will benefit from the MCRC's excellent core facilities, present your work at conferences, and gain experience in patient and public involvement, all within a collaborative, translationally focused, state-of-the-art research environment, while contributing directly to the development of more effective treatments for women with gynaecological cancers. Eligibility You must hold, or about to obtain, a minimum Upper Second Class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. A related master’s degree would be an advantage International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University's Country Specific information page. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply Apply directly via this link: https://tinyurl.com/577zjazd or on the online application portal, select MCRC PhD Programme as the programme of study. You may only apply for one project within this scheme. Please ensure that your application includes all required supporting documents: Curriculum Vitae (CV) Supporting Statement Academic Certificates and Transcripts Incomplete or late applications will not be considered. Further details are available on our website: CRUK Manchester Centre PhD Training Scheme | Biology, Medicine and Health | University of Manchester Application Timeline Applications open: Monday, 5 October 2026 Application deadline: Monday, 23 November 2026 Interview date: Week commencing 11 January 2027 Start date: September 2027 Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study/research/getting-started/equality-diversity-inclusion/

Research areas