Control of apoptosis during mitosis and in response to anti-cancer drugs

Cancer chemotherapeutic drugs such as taxol (paclitaxel) and vinca alkaloids target dividing cells by interfering with the function of the mitotic spindle, thereby inhibiting cell proliferation and inducing cell death by the process of apoptosis. These drugs are often effective in treating cancers but their use is limited by toxic side effects and the development of resistance. In order to improve their use, we need to understand the mechanisms that determine how cancer cells react to these drugs. Our recent work has identified a new signalling pathway that controls the response of cells to disruption of the mitotic spindle by taxol. This pathway is controlled by the oncogenic protein, Mcl-1, and is likely to be suppressed in many cancer cells. In this project we will investigate the control of this pathway through the mechanisms of protein phosphorylation and ubiquitin-proteasome mediated proteolysis. We will use biochemical approaches and advanced cell imaging to study the pathway in individual cells. We will also investigate how to manipulate this pathway in order to sensitise cancer cells to cell killing by chemotherapy. This project therefore has the potential to improve the efficacy of anti-cancer drugs, reduce side effects on non-dividing cells and facilitate new strategies for the selective destruction of cancer cells. 


First/upper second class BSc or Masters degree in a biological science

Professor Paul Clarke
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This project is open to self-funding students and students eligible for CRUK Funding.