What happens when mitosis fails

Professor Paul Clarke
Director, Diamantina Institute
The University of Queensland

Abstract: Defects in chromosome segregation during mitosis can result in aneuploidy and chromosome instability, which is associated causally with cancer. The propagation of chromosome abnormalities is normally restricted by the induction of cell death in cells that fail to complete mitosis. We show that mitotic cell death is linked to the progression of mitosis through protein phosphorylation and protein degradation, and is under the control of the products of oncogenes and tumour suppressors. We also show that cells which escape mitosis after a disruption have a sustained stress response that determines cell fate. These mechanisms may provide opportunities to enhance the response of cancer cells to chemotherapy.

Bio: Paul Clarke is Director of the University of Queensland Diamantina Institute. He joined UQ in 2017 from the University of Dundee in Scotland where he was Professor of Cancer Cell Biology and Associate Dean (Research) in the School of Medicine. He was lead for Dundee's submission to the UK Research Excellence Framework (REF2014) in Clinical Medicine, which scored a maximum 4* rating and was rated first equal in the UK for the research impact. He joined the University of Dundee as a Senior Lecturer in 1998 and was awarded a personal chair in 2005. Previously he was a postdoctoral research fellow working on control of the cell cycle in the group of Eric Karsenti at the European Molecular Biology Laboratory, Heidelberg (1991-1994) and a senior research fellow at the University of Manchester (1994-1998). As an undergraduate, he read Biochemistry at the University of Bristol and, for his PhD, carried out research on the control of metabolism by the AMP-activated protein kinase with D. Grahame Hardie FRS at Dundee. Professor Clarke has received a Royal Society-Wolfson Research Merit Award (2003-2008) and research fellowships from The Wellcome Trust and Cancer Research UK. He has served on grant review panels for MRC, BBSRC and Cancer Research UK in the UK and several other panels across Europe. Professor Clarke's current research interests are the molecular mechanisms of cell division, chromosome instability and mitotic cell death. He also carries out research into the cellular responses to anti-cancer drugs.