Modeling and Analysis of Mitotic Microtubule Dynamics

描述（由申请人提供）：着丝点微管（kmt）介导纺锤极和染色体之间的附着，促进有丝分裂过程中染色体的运动和组织。计算机建模可用于弥合有丝分裂纺锤体表型的实验分析和介导染色体组织的潜在kMT动力学之间的差距。先前，我们确定了一个中期kMT动力学调节模型，该模型结合了微管突变频率的空间梯度和张力依赖的救援频率。在这项工作中，我们将使用先前开发的方法结合新的实验和特定突变来测试这些模型预测。具体来说，我们将测试着丝点张力调节中期kMT动力学的假设，并建立对着丝点在调节微管动力学中的作用的理解。

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.