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。它是基于由动态生物聚合物和分子马达组成的复杂的机械化学机。我们专注于一种这样的机器，有丝分裂纺锤体，它从微管和多个马达自我组装成双极结构。马达和微管都会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，目前的挑战是了解单个组件的活动是如何协调的，以生产一台能够以细胞中观察到的保真度分离染色单体的精密机器。 研究人员将使用数学分析、计算机模拟和实验的新组合来开发有丝分裂纺锤体的解释性和预测性定量模型。确定性和随机性模型将被开发、分析和计算机模拟。建模的目的是：1.分析微管和多个马达在纺锤体形态发生中的作用；2.阐明微管和多个马达自组织成有丝分裂纺锤体样结构的机制；3.分析微管和多个马达在染色体定位中的作用；4.模拟肌动球蛋白收缩和微管运动依赖的运输在细胞质分裂中的相互作用。研究人员将使用显微镜、遗传和生化技术来获得验证模型所需的数据。 定量模拟结合实验将阐明有丝分裂纺锤体的时空组织和调控原理。这些模型将允许测试有丝分裂和细胞分裂的合理情景。它们将为理解和预测重要生物医学环境中的动态细胞行为提供一个新的跨学科水平。

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.