Modeling and Analysis of Mitotic Microtubule Dynamics

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DESCRIPTION (provided by applicant): Kinetochore microtubules (kMTs) mediate attachments between spindle poles and chromosomes, facilitating the movement and organization of chromosomes during mitosis. Computer modeling can be used to bridge the gap between experimental analysis of mitotic spindle phenotypes and the underlying kMT dynamics that mediate chromosome organization. Previously, we identified a model for regulation of metaphase kMT dynamics that combines a spatial gradient in microtubule catastrophe frequency with a tension dependent rescue frequency. In this work, we will test these model predictions using previously developed methodologies combined with new experiments and specific mutations. Specifically, we will test the hypothesis that tension at the kinetochore regulates kMT dynamics during metaphase, and build an understanding of the role of the kinetochore in regulation of microtubule dynamics.