Chromosome segregation, aneuploidy and cancer
An important source of the genomic damage associated with both aging and cancer is the accumulation of aneuploidies due to chromosome missegregation. In healthy cells, accurate chromosome segregation is normally ensured by the spindle assembly checkpoint. By contrast, in cancer cells, the spindle checkpoint fails to prevent abnormal segregation events, leading to highly aneuploid genomes. But how do cancer cells tolerate and proliferate despite these abnormal genomes? To understand this, a major interest of the lab focuses on p38-dependent stress response pathway that activates the p53 tumour suppressor in response to dramatic changes in gene dosage. Our second major interest is based on the fact that several widely used anti-cancer drugs and 2nd chemotherapeutics kill cancer cells by activating the SAC. But how does a prolonged mitotic arrest lead to cell death? To understand this we are dissecting the factors that dictate the balance between “death in mitosis” and “slippage”, whereby cells exit mitosis, return to interphase and survive. A genome-wide siRNA library screen has identified a transcription factor that plays a key role promoting “death in mitosis”. We are now delineating the apoptosis pathways that connect this transcription factor with mitotic cell death. For more information on the lab, see www.bub1.com.
This project has a Band 2 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.
•Gascoigne, K.E., and Taylor, S.S. (2009). How do anti-mitotic drugs kill cancer cells? J Cell Sci 122, 2579-2585.
•Lara-Gonzalez, P., Westhorpe, F.G., and Taylor, S.S. (2012). The Spindle Assembly Checkpoint. Current Biology 22, R966-R980.
•Topham, C.H. and Taylor, S.S. (2013) Mitosis and apoptosis: how is the balance set? Curr Opin Cell Biol, 25:780-785.