A hallmark of mitosis in mammalian cells is the alignment of chromosomes into a thin metaphase plate. This conserved, reproducible structure probably arises from a coordinated interaction between dynamic microtubule ends, kinetochores, molecular motors, centromeric chromatin, and the spindle checkpoint machinery, but the contributions of these different components has been difficult to discern. Our lab is interested in understanding how this structure forms, and how the individual molecules and structures contribute to the formation of the metaphase plate. We have used a variety of tools to examine this question—proteomic analysis of chromatin at defined cell cycle states, analysis of post-translational modifications, high spatial and temporal resolution fluorescence imaging in fixed and living cells, and the development of software tools to visualize, manage, and analyse the complex datasets that this work generates. I will describe our latest results that reveal new regulatory mechanisms that control the assembly and dynamics of mitotic spindles and microtubule-kinetochore attachments. I will focus on the function and roles of Bod1, a PP2A-B56 inhibitor, that controls the function of mitotic centrosomes and kinetochores, and its relative Bod1L that interacts with PP2A-B56 and modulates the DNA damage response. I will also briefly mention our efforts to develop standardized interfaces for biological imaging. This project, the Open Microscopy Environment (http://openmicroscopy.org), is an open source, community-led development effort that delivers data models, file specifications, and data management software for biological microscopy.
Lunch @ 11:45, seminar 12-1:00