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Ubiquitin-mediated signaling in cell division

 

Dr Catherine Lindon - Group leader

Fellow of Newnham College
E-Mail: a
Tel: +44 1223 333964/Lab: 765927

Keywords

Ubiquitin, APC/C, Aurora kinase, cell cycle, PROTACs

 

Investigator biography

Cath discovered her interest in cell biology at the Institut Pasteur in Paris, during postdoctoral studies of myogenic cell fate control. She returned to the UK with a Wellcome Trust Advanced Training Fellowship, to acquire expertise in cell cycle research with the Pines group at the Gurdon Institute in Cambridge. She subsequently set up her own research programme to study ubiquitin-mediated protein degradation in mitotic exit, with the support of a Career Development Award from the MRC. In 2008 she became a research group leader in the Department of Genetics and in 2015 took up a lectureship in the Department of Pharmacology.

 

Research summary

In the @LindonLab we study ubiquitin pathways regulating the cell cycle in human cells. Ubiquitination of target proteins triggers their destruction at the 26S proteasome, and ubiquitination mediated by the Anaphase-Promoting Complex (APC/C) ubiquitin ligase is one of the key pathways regulating mitosis. Aurora kinases are important substrates of the APC/C and many of the projects in our lab study Aurora A kinase (AURKA), both as a model substrate of the APC/C that can be used to study substrate-specific determinants of APC/C activity, but also as a major regulator of the cell cycle whose activity levels are an important output of APC/C activity in interphase. Overexpression of AURKA is strongly associated with several types of cancer, and this kinase is a well-known therapeutic target in cancer drug development. No AURKA inhibitor has yet reached the clinic, but the specific inhibitor alisertib is a useful tool for cell biology. Our recent work has characterized the behaviour of small molecule PROTACs bearing an alisertib 'warhead' that can be used to eliminate excess AURKA from the cell using the new therapeutic strategy of targeted protein degradation (TPD). Other projects in the lab are developing new approaches to image protein stability in single cells through use of tandem fluorescent protein tags (in collaboration with AstraZeneca), and generating new TPD tools (in collaboration with the Itzhaki Lab) with the aim of harnessing the activity of the APC/C in PROTAC design.

Our research is currently funded by the BBSRC, Royal Society, AstraZeneca and  Rosetrees Trust. We acknowledge the MRC and Cancer Research UK for past support.