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Research Interests

 

 

New pages coming.

Until then, please visit our pages at the Department of Genetics.

We study cell division in human cells. We are working to understand the contribution of ubiquitin-mediated signaling to the outcomes of mitotic cell division, when the two daughter cells rapidly return to the interphase state that follows mitosis, through targeted inactivation and/or destruction (via ubiquitin-mediated proteolysis) of dozens of key proteins. This is a period of intense reorganization of cellular components. As well as ensuring that an identical copy of the genome is delivered to each daughter cell, ubiquitin-mediated signaling contributes to extensive reorganization of the cell cytoskeleton and organelles such as the mitochondria that are also inherited by daughter cells. We are working to identify the ubiquitin-mediated signals involved and to understand how they can influence the fate of daughter cells.

Our research approach examines ubiquitination and proteostasis using cell-based assays that complement our imaging approaches to the study of cell behaviour. We use time-lapse imaging of living cells both to measure substrate proteolysis and to examine its outcomes, alongside biochemical strategies to ‘capture’ ubiquitination events in cell division. We are also working to develop new approaches to imaging dynamic ubiquitin-dependent processes in single cells.

One model substrate we study in detail is Aurora kinase A, a key regulator of the cytoskeleton during cell division and a well-known target of the anaphase promoting complex (APC/C) ubiquitin ligase at the end of mitosis. Deregulated Aurora A is a common driver of cancer and a current focus in the development of new therapeutic tools. We aim to delineate the dynamic relationship between proteolysis and function of Aurora A.