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Mathematical Modeling and Experimental Approaches Reveal Novel Roles of Cortical Dynein in Spindle Dynamics and Centrosome Clustering

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Faithful cell division requires the mitotic spindle, a tightly regulated biophysical machine composed of rigid microtubule filaments along with motor and non-motor proteins. A balance of forces on and within the spindle structure is required for efficient and error-free cell division. A key player in this balance of forces is dynein, a motor protein whose localization and function at the cell cortex regulates spindle positioning and orientation. By creating a mathematical and computational model to capture spindle formation and maintenance, I have found novel dynein-dependent force contributions to bipolar spindle dynamics. I use biological experimentation to both inform and validate the model, and confirm that dynein-derived forces impact spindle dynamics in cells. Furthermore, I use a combined experimental-modeling approach to explore the role of dynein in cells with multipolar spindles, an alteration to spindle morphology that is common in cancer cells. Through this work I find that dynein-derived forces may be important for the continued proliferation of cancer cells with multipolar spindles. Studying the physical forces driving division in cells with altered spindle structure provides insight into potential drug targets to prevent cancer progression.

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  • etd-69841
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  • 2022
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  • 2022-05-31
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  • etd-69841
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  • 2022-12-09

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