Data-driven probabilistic modelling of clonal dynamics in human tissues and cancers

Cancer is responsible for one in eight deaths, worldwide. Cancer initiation and development is driven by the accumulation of genetic mutations within cells that maintain and regenerate human tissues. In the last decade, rapid advances in next-generation genome sequencing technologies have re-shaped the way we think about this mutational process. Both cancer and tissues from healthy individuals are now known to be a mosaic of genetic “clones”, each clone derived from a single common ancestor cell carrying a mutation similar to the way that mutation and selection govern the evolution of species. Recently, scientists have employed mathematical modelling in combination with probabilistic inference to elucidate the dynamics of clonal evolution over the course of a human lifetime. Such work has revealed an intricate balance of cellular interactions within human tissues, which can be perturbed by certain mutations to drive the emergence of cancer.

This project will develop and extend the above computational and mathematical analyses of clonal dynamics to different tissue and cancer types, including cancers of the colon, intestine and endocrine glands. Depending on your interests and experiences, approaches used may include: 1) statistical analysis of “big data” coming from clinical genomics, 2) stochastic modelling of clonal dynamics, 3) Bayesian inference from experimental cell lineage tracing and imaging data. The project is therefore suitable for students with a background in (but not limited to):

• Applied Mathematics or Theoretical Physics

• Computational Biology or Bioinformatics

• Computer Science or Engineering

Proficiency in at least one programming language is a requirement. While having a base in the School of Mathematics in Birmingham, you will join a research team that also includes world-leading clinicians and experimentalists, alongside established collaborations in Cambridge, London, Germany and Spain working together at the forefront of cancer research.