Molecular Mechanisms of Cell Death

Diseases such as cancer and neurodegenerative disorders are characterised by a significant alteration in the total number of cells within the tissue. This may result from increased division of cells and/or may arise from a defect in cell death regulation. In tissues, such as the lymphoid system or the colon, cell death is very important as it controls the total number of cells within that tissue, whereas in the nervous system inappropriate cell death is catastrophic. Consequently, cell death in these situations is tightly controlled and often occurs in an ordered manner by a process called ‘apoptosis’, or a more recently identified mode of cell death termed ‘necroptosis’. We are studying these cell death processes because to successfully treat many diseases (e.g. cancer) it is important that we find ways to switch ‘ON’ cell death. However, it is crucial to first understand the basic mechanisms that regulate cell death in order to identify ways of selectively killing target cells while leaving most healthy cells unharmed. We are therefore trying to understand the fundamental mechanisms that regulate the response of target cells and normal cells to cytotoxic agents, as this will help in establishing the ideal choice agents for the treatment of disease. Our aim is to establish better predictive models of mitochondrial toxicity, providing mechanistic frameworks to facilitate safer drug development and potentially alleviate the toxic effects of existing treatments.