Dissecting clonal heterogeneity with cellular lineage tracing in cancer and development
Supervisor: Professor Martin Taylor
Both tumours and organisms grow through the binary division of cells, producing clonal lineages in which relationships between cells can be described with bifurcating trees. The branches of these trees can be uniquely labelled by new mutations arising during clonal growth. This principal underpins approaches to infer the sequence of cell-type changes through developmental lineage tracing, and the modelling of tumour evolution. Our recent work (PMID:32581361) revealed the frequent occurrence of lesion segregation – where unrepaired DNA damage can segregate through multiple cell divisions. This finding undermines key assumptions of previous lineage tracing approaches but also offers opportunities for higher resolution lineage tracing than has previously been possible. This project will develop the mathematical and computational tools to utilise lesion segregation for accurate linage resolution and apply them to the analysis of whole genome sequence and single cell sequencing data from in vitro and in vivo models of clonal growth and human cancer genome data. The project would suit PhD candidates with a background in quantitative sciences and would be analysis based as primary data is in hand, though new data can generated or commissioned to support the project as it develops.