The role of the p53 co-factor JMY in the regulation of gene expression in human cancer

Tumour growth is achieved by overriding cell cycle control and bypassing cell death mechanisms. Mechanisms influencing cell survival such as apoptosis and autophagy are key determinants of cell fate during stress. Moreover, during tumour progression the acquisition of metastatic potential is the most devastating event in human cancer with metastatic disease the cause of 90% of cancer deaths. Importantly, understanding how the cell integrates a variety of signals to affect a cellular outcome is clinically relevant and a poorly understood process.

p53 is a nuclear transcription factor that plays a pivotal role in the prevention of human cancer in part through its role during cellular stress which results in a variety of outcomes such as cell cycle arrest, autophagy or apoptosis. The critical importance of p53 function is highlighted by the fact that the majority of human tumours harbour compromised p53 activity. JMY is a p53 transcriptional co-factor that accumulates in the nucleus during the DNA damage response to influence p53-dependent apoptosis. This project will investigate the nuclear targets of JMY in order to identify genes whose activity influences cell fate during the stress response and the mechanisms involved. This work will involve a range of cell and molecular biology techniques including RNA-Seq, bio-informatics, microscopy, cell-based assays and chemical biology techniques.

An appropriate student will have a good background in biochemistry and cell biology together with an enthusiasm and strong desire to understand molecular mechanism related to cancer biology.

Applicants should hold, or be expected to hold, a Master’s degree with a minimum of a commendation, and/or a 1stClass / 2.1 Bachelor’s Honour’s Degree (or UK equivalent) in Cell Biology, Biochemistry, Molecular Biology, or a related Biosciences related subject.