Tracing the dynamics of epithelial cell competition in normal and perturbed states

Epithelia comprise a variety of specialised differentiated cell types that ensure a diversity of functions. To ensure their maintenance, epithelia constantly renew, replacing cells lost through exhaustion or damage. This process is undertaken by stem cells – specialised tissue-specific cells – that renew through division, while giving rise to differentiating progeny. A key challenge in epithelial biology is to understand how stem cells maintain the balance between proliferation and differentiation, and how these programmes become corrupted during tumour development. 

We will use a new transgenic mouse model in which the random induction of fluorescent reporter genes allows the fate of individual cells to be tracked. By coupling the red reporter with the activation of cancer genes, we will use quantitative modelling to define the changes that take place in cell fate following the acquisition of mutations, targeting tumour cells and the reaction of surrounding tissue.