Resolving the evolutionary dynamics of renal cancer metastases and therapy resistance

This 4-year PhD studentship is offered in Dr Samra Turajlic’s Group based at the Francis Crick Institute (the Crick).

Evolutionary principles are increasingly applied to help us understand cancer initiation and progression as evidence by our work to date [1-4]. In the context of renal cancer we observe that the mode of evolution can determine the growth of the primary tumour and the patterns of metastatic progression. Renal cancer in particular exhibits a wide range of metastatic phenotypes- from very latent metastases with predilection for endocrine tissues; oligometastases where metastases are confined to a single organ; and widespread/rapid metastases. To build on this we will decipher the evolutionary dynamics of renal cancer metastases, characterizing the sources of selection that lead to emergence of metastasis-competent clones at the site of the primary tumour; understand the patterns and timing of metastatic spread; identify novel/common vulnerabilities within the metastatic process, that may inform new strategies for therapeutic targeting; and understand the mechanisms of resistance to targeted and immune-oncology agents. This is very pertinent in the context of renal cancer because the therapies used to treat the disease target the tumour microenvironment (angiogenesis or immune cells).
Through a established research studies: TRACERx Renal and a post-mortem (PEACE) Study, there is a unique opportunity to sample a whole range of metastatic sites. The TRACERx Renal study has complete recruitment and we have already performed 20 renal cancer post-mortem with both studies contributing 100s of samples that undergo whole exome, genome and RNA sequencing, generating the largest dataset of this type worldwide. This is an opportunity to work with this dataset to provide unprecedented insights into patterns of renal cancer spread and the variation in evolutionary patterns between cases.

Understanding evolutionary dynamics in renal cancer also has the potential to inform design of future clinical trials with regards to the timing of therapy. The current paradigm rests upon an assumption of linear progression and will be challenged in this project.

The candidate will be based in a multi-disciplinary team of cancer evolutionary biologists and translational research clinicians concerned with both basic evolutionary principles and application of evolutionary rules in the clinic. We collaborate nationally and internationally and there will be ample opportunities for training at the Crick and beyond.

Candidate background

This project would suit a candidate with a background in mathematics, physics, statistics, bioinformatics, evolutionary biology who has an interest in cancer evolution, cancer biology and translational research. Prior experience of computational methods especially in cancer genomics and cancer evolution is useful, but ample opportunities for training will be provided to those without such experience.

Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2021 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.

APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE https://www.crick.ac.uk/careers-and-study/students/phd-students BY 12:00 (NOON) 12 November 2020. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.