We analyse the protein networks controlling chromosome segregation to understand how the wiring of these networks and the interplay of their components ensure error-free chromosome segregation. Our focus is the regulation of the transition from metaphase to anaphase: we aim to elucidate how this crucial step in the cell cycle is controlled by the spindle assembly checkpoint, what makes it rapid and synchronous for all chromosomes, and how the segregation of chromosomes is coordinated with other cellular events. Through understanding this particular, highly orchestrated and essential process, we aim to uncover general principles of cellular information processing that will allow us to comprehend and eventually control cellular behavior.
The spindle assembly checkpoint is a conserved signaling pathway that is crucial for the faithful inheritance of chromosomes. This checkpoint is able to rapidly respond to changes in chromosome attachment in a highly sensitive but robust manner. To elucidate the molecular basis of these attributes, we employ a combination of quantitative live cell fluorescence microscopy, quantitative biochemical methods and mathematical modeling, using fission yeast (Schizosaccharomyces pombe) as a model organism. We bring the same spectrum of methods to the analysis of anaphase onset, where the slow degradation of an anaphase inhibitor results in very rapid, synchronous splitting of sister chromatids.
In a second line of work, we have identified substrates of one of the master regulator kinases of cell division, Aurora. Aurora is known to control chromosome segregation. Our results suggest that Aurora has a more widespread role in mitosis and cell cycle progression, which we aim to elucidate.
Cells expressing GFP-tagged spindle assembly checkpoint proteins (left side) and the interaction network of these proteins (right side).
Cells synchronously progressing through the cell cycle (left side) were analyzed by quantitative mass spectrometry to reveal the fluctuation of Aurora-dependent phosphorylation sites during the cell cycle (right side).