Dynamics of Mitotic Spindle Morphogenesis.

描述（由申请人提供）：细胞分裂是细胞行为的一个基本的重要例子。它基于由动态生物聚合物和分子马达组成的复杂机械化学机器。我们重点研究了一种这样的机器，有丝分裂纺锤体，它由微管和多个马达自组装成双极结构。马达和微管都产生协调的力量和运动，并控制染色体分离和细胞内运输。考虑到纺锤体中丰富的微管和运动功能，当前的挑战是了解单个组件的活动如何协调，以产生能够分离染色单体的精密机器，并达到在细胞中观察到的保真度。

DESCRIPTION (provided by applicant): Cell division is a fundamentally important example of cell behavior. It is based on complex mechanochemical machines consisting of dynamic biopolymers and molecular motors. We focus on one such machine, mitotic spindle, which self-assembles into a bipolar structure from microtubules and multiple motors. Both motors and microtubules generate coordinated forces and movements and govern chromosome separation and intracellular transport. Given this rich repertoire of microtubule and motor functions in the spindle, a current challenge is to understand how the activities of the individual components are coordinated to produce a precision machine capable of segregating chromatids with the fidelity observed in cells. The investigators will use a novel combination of mathematical analysis, computer simulations and experiment to develop explanatory and predictive quantitative models of mitotic spindle. Deterministic and stochastic models will be developed, analyzed and computer simulated. The modeling aims are 1. To analyze the roles of microtubules and multiple motors in spindle morphogenesis, 2. To elucidate mechanisms of self-organization of microtubules and multiple motors into mitotic spindle-like structures, 3. To analyze the roles of microtubules and multiple motors in chromosome positioning, 4. To model interaction between actomyosin contraction and microtubule-motor-dependent transport in cytokinesis. The investigators will use microscopy, genetic and biochemical techniques to obtain data needed to validate the models. Quantitative modeling complemented by experiments will elucidate principles of spatio-temporal organization and regulation of mitotic spindle. The models will allow to test plausible scenarios of mitosis and cell division. They will provide a new interdisciplinary level of understanding and predicting dynamic cell behavior in important biomedical situations.