Primary Supervisor: Dr Tim Fenton (University of Kent)
Dr Maria Emanuela Cuomo, Associate Director, UK Lead for Cell Biology and Genome Editing / CRISPR (AstraZeneca)
Prof Michelle West (University of Sussex)
APOBEC3A (A3A) deaminates cytosine to uracil in RNA and single-stranded DNA; limiting replication of viruses and endogenous retroelements and playing a crucial role in preserving cellular integrity. Off-target consequences of this anti-viral activity can result in somatic mutations that promote carcinogenesis but despite its functional importance, very little is known regarding A3A regulation. This project (a CASE studentship with AstraZeneca) will use cutting-edge technologies including circular chromatin confirmation capture (4C) to identify A3A enhancer elements and lentiviral CRISPR library screening to map critical transcription factor binding sites responsible for A3A induction in epithelial cells during growth factor signalling and human papillomavirus infection.
Determining how A3A gene expression is controlled will further our understanding of its role in normal cells and will provide clues as to how regulation is lost during carcinogenesis, resulting in APOBEC-induced mutations: the ‘friendly fire’ that fuels development and progression of many cancers.