Mechanisms safe-guarding genome integrity during mammalian cell division

The accurate partitioning of chromosomes to daughter cells in mitosis is essential for ensuring the viability of cells, tissues, and organisms. Defects in this process lead to genomic instability - manifesting as cell death and diseases such as cancer. Eukaryotic cells employ a molecular surveillance mechanism, the "spindle assembly checkpoint" (SAC), to monitor the proper attachment of chromosomes to the mitotic spindle via structures called kinetochores - thus ensuring faithful segregation of the genome during mitosis. While the broad principles of the SAC are known, some of the molecular details about how SAC proteins interact and fulfil their function is still lacking. In particular, it is incompletely understood precisely how improperly attached kinetochores recruit and activate key SAC regulators to turn on the spindle assembly checkpoint. This project seeks to study, in vivo and in vitro, the interaction of the mammalian master SAC kinase MPS1 with kinetochores. A range of multidisciplinary techniques including fluorescence microscopy, genetic engineering, and protein biochemistry will be used to study MPS1 and downstream SAC proteins of interest. Quantitative image processing and statistics will serve as key skills for the analysis of datasets.