Delineating NuRD complex commitments through chromatin dynamics in driving epithelial to mesenchymal transition during cellular reprogramming

We showed that specialised skin cells that lack individual NuRD components influence EMT and cell fate, and they might represent a unique chromatin signature during cell physiology. We will examine how NuRD complex constitute the blueprint for a better understanding of chromatin remodeling by NuRD during the EMT process.

To date, much is known of the role of chromatin remodelers such as Nucleosome Remodeling and histone Deacetylase (NuRD) during epithelial to mesenchymal transition (EMT) in a number of pathologies. EMT is critically important during physiology and cell differentiation therefore we need to understand the mechanistic importance of NuRD in normal physiology.

Our preliminary data demonstrated that individual NuRD subunits are implicated in diverse cell cycle stages, suggesting that distinct NuRD subunits have discrete functions of relevance to EMT and cellular homeostasis. In order to determine the impact of chromatin remodelers on cell differentiation, we will (re)evaluate the pleiotropic roles of EMT master regulators together with NuRD and elucidate their contribution to (1) cell-fate specification/transition, (2) cell proliferation/self-renewal capacity, and (3) chromatin/epigenetic (re)programming. To unravel key chromatin and epigenetic modifiers in a fully integrated study of cellular differentiation, we will combine molecular biology, classical biochemistry, chromatin assays, cell physiology, unbiased proteomics and functional genomics.

Our work will constitute the blueprint for a better understanding of how nuclear chromatin is remodelled by NuRD during the EMT process. Thus, aiding researchers to better understand EMT not only in normal physiology but will underpin discoveries in regenerative medicine, cancer, wound healing and development.

Eligibility for a full DfE studentship requires you to have been resident in the United Kingdom for a three-year period before the first day of the first academic year of the course. You must hold or expect to gain an upper second-class honours degree.