Biological Sciences

Events and seminars

Monday Seminar Series - "Cell Cycle Control of Chromosome Segregation: Focus on Kinetochores and Centrosomes"

Professor Erich Nigg - Biozentrum, University of Basel

13th February 2017 at 12:00pm [Download iCalendar / .ics file]

Daniel Rutherford, G.27, LT1

The error-free segregation of duplicated chromosomes during cell division is crucial to the development and health of all organisms. Conversely, chromosome mis-segregation is held responsible for causing human disease, including cancer. Chromosome aberrations are thought to result from the deregulation of mitotic progression, a defective spindle assembly checkpoint, and/or centrosome abnormalities. Our laboratory is interested in the cell cycle control of chromosome segregation, with particular emphasis on the function of kinetochores and the regulation of the centrosome duplication cycle. In the first part of my talk, I will briefly summarize our recent work on the role of the Ska complex in mediating kinetochore-microtubule interactions during mitosis. Our results lead us to propose that the Ska complex promotes Aurora B activity to limit its own microtubule and kinetochore association, thereby ensuring that the dynamics and stability of kinetochore microtubules fall within an optimal range for chromosome bi-orientation on the spindle apparatus.In the second part of my talk I will focus on the centrosome duplication cycle. Centrosomes organize microtubule arrays important for cell shape, polarity and motility as well as chromosome segregation. Moreover, the core components of centrosomes, the centrioles, are essential for the formation of cilia. Centrosome and centriole aberrations have been implicated in tumorigenesis, ciliopathies, microcephaly and dwarfism. I will briefly summarize our current understanding of the mechanism underlying centriole duplication in human cells, with particular emphasis on a core module that comprises the protein kinase Plk4, its substrate STIL, and the cartwheel component Sas-6. I will then focus on the regulation of STIL abundance during the cell cycle, and present data that lead us to propose that centriole amplification may constitute one root cause of primary microcephaly. Finally, I will summarize our recent work aimed at a quantitative understanding of centrosome architecture. To measure the abundance of key centrosomal proteins within cells and at the centrosome, respectively, we have combined targeted proteomics with EGFP-tagging of selected proteins at endogenous loci. Our results provide a first assessment of the absolute and relative amounts of major components of the human centrosome.

Host JP Arulanandam

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