UCL Cancer Institute

Thursday 24th May at 5pm in the Courtyard Café, Paul O’Gorman Building

Professor Jon Pines   –  The Gurdon Institute, University of Cambridge

“Cell division: ensuring 92 ÷ 2 always = 46 in mitosis“

How do cells regulate entry to mitosis? And, once in mitosis, how do cells coordinate chromosome segregation with cell division (cytokinesis) to ensure that the two daughter cells receive an equal and identical copy of the genome? The answer lies in the interplay between protein kinases, protein phosphatases, and APC/C-mediated proteolysis, and this is the focus of our research. Because mitosis is a highly dynamic process we study living cells by time-lapse fluorescence microscopy but to complement this with biochemical analyses we are using somatic cell recombination to knock-out and mutate specific mitotic regulators.This has given us remarkably accurate and precise in vivo kinetics for protein degradation.
Using both in vitro cell biological and in vivo techniques coupled with analysis of primary patient tumour material the lab is seeking to answer three questions:-

To understand how cells initiate mitosis we are analysing the behaviour of the key mitotic kinases, the Cyclin A- and B-dependent kinases, and their regulation by phosphorylation and dephosphorylation.We recently developed a FRET biosensor to assay Cyclin B1-Cdk1 activity in vivo and are using this to define the pathways that regulate the timing of mitosis.To identify the proteins responsible for regulating the Cyclin-Cdks, and provide insights into Cyclin-Cdk substrates, we have analysed protein complexes through the cell cycle by SILAC mass spectrometry and are following up some of the exciting results from this screen.

To understand how proteolysis regulates progress through mitosis we complement the analysis of APC/C-dependent degradation in living cells with biochemical analyses of protein complexes and ubiquitination activity.These studies are revealing how the APC/C is activated and how it is able to select a particular protein for destruction at a specific time. Our research is also providing insights into how APC/C activity is regulated by the spindle assembly checkpoint that is essential to the control of chromosome segregation and cytokinesis. In particular, we are beginning to elucidate the key events in the checkpoint pathway and their antagonism by the APC/C itself.

More information on Professor Pines’s research can be found at: http://www.gurdon.cam.ac.uk/~pineslab/New_Web_Site/Site/Welcome.html

Host: Professor Hiro Yamano – Please contact Professor Hiro Yamano if you wish to meet with the speaker.

All are welcome. A reception will be held after the seminar.