Steve Jackson

This PhD project at the University of Cambridge investigates the mechanisms underlying cancer cell responses to Targeted Alpha Therapy (TAT), a cutting-edge approach that delivers high Linear Energy Transfer (LET) alpha-particles to cancer cells, aiming to maximize therapeutic efficacy while minimizing toxicity. While much is known about radiation sensitivity in the context of low-LET radiation, the genetic and cellular determinants of sensitivity to high-LET radiation, such as that used in TAT, remain largely unexplored. Recent findings suggest that some cancer cells exposed to alpha particles may survive with sub-lethal DNA damage, presenting an opportunity to enhance treatment by combining TAT with DNA-damage response (DDR) inhibitors. The successful candidate will use established human cell models to explore the effects of radioligand therapies on cell viability and DDR activation. The project involves performing CRISPR screens to identify genetic factors influencing resistance or sensitivity to TAT, followed by mechanistic studies of promising targets. These investigations may reveal new biomarkers, therapeutic vulnerabilities, and mechanisms of cellular response relevant to both normal and tumor cells. The research is supported by references to recent high-impact publications in Nature Reviews Molecular and Cell Biology, Nature Communications, Cancer Research, Scientific Reports, and Radiotherapy and Oncology. Applicants should possess excellent laboratory skills and a strong background in biochemistry, molecular biology, and genomics. Prior research experience is highly valued. The position is open to UK citizens, overseas students meeting UK residency requirements, or those able to secure additional funding to cover international fee differences. Funding includes a four-year stipend, tuition fees at the Home rate, and support for project consumables and training. The application deadline is 17th October 2025, with interviews scheduled for early January 2026. The University of Cambridge is committed to equality, diversity, and inclusion, and encourages applications from all backgrounds. For application, use the University Applicant Portal and quote reference SW47205.