A Molecular Study of Min-Protein Polymer Dynamics

描述(申请人提供)：在大肠杆菌和相关细菌中，细胞分裂的显著准确性部分受MinProtein系统的调节，该系统通过在空间上从一极到另一极的振荡来防止细胞末端附近的分裂。这位科学家最近开发了一个完整的Min系统模型，只使用了蛋白质的已知属性，它准确地再现了观察到的振荡，并预测了Mind蛋白质的有限核苷酸交换率约为一秒，这个数字后来得到了实验验证，具有很高的准确性。这项提议涉及在杆状细胞中开发粒子级模拟的努力，以首次捕捉Min蛋白质的螺旋聚合物动力学。此外，这位科学家打算将该模型扩展到圆形细胞，以确定在存在统计波动的情况下，Min振荡是否可以自发地选择细胞的长轴来定义球菌的分裂平面。这些粒子水平的模拟为一般理解原核生物和真核生物如何利用反应扩散蛋白质系统将蛋白质靶向不同的位置并检测它们自己的几何形状提供了一个起点，并将在大规模计算和蛋白质相互作用的微尺度生物学之间的不断扩大的接口上有广泛的应用。为了了解大肠杆菌令人难以置信的分裂精度背后的机制，科学家将进行结合计算结果的实验，研究浓度变化对振荡周期和分裂精度的影响。这项理论工作将在普林斯顿大学内德·温格伦博士的实验室进行，普林斯顿大学的邦妮·巴斯勒博士将提供实验资源和培训。

DESCRIPTION (provided by applicant): The remarkable accuracy of cell division in E. coli and related bacteria is partially regulated by the Minprotein system, which prevents division near the cell ends by oscillating spatially from pole to pole. The scientist has recently developed a complete model of the Min system, using only known properties of the proteins, which accurately reproduces the observed oscillations and predicts a finite nucleotide exchange rate for the MinD protein of around one second, a number that has since been experimentally verified to a high degree of accuracy. This proposal concerns efforts to develop particle-level simulations in rod-shaped cells, to capture for the first time the helical polymer dynamics of the Min proteins. In addition, the scientist intends to extend the model to round cells, to determine whether Min oscillations can spontaneously select the long axis of the cell to define the division plane in cocci in the presence of statistical fluctuations. These particle-level simulations provides a starting point for a general understanding of how prokaryotes and eukaryotes can use a reaction-diffusion protein system to target proteins to different locations and to detect their own geometry, and will have broad applications at the expanding interface between large-scale computation and the microscale biology of protein interactions. In order to understand the mechanism behind E. coli's incredible division accuracy, the scientist will undertake experiments incorporating computational results to study the effects of changes in concentration on oscillation period and division accuracy. The theoretical work will be performed in Dr. Ned Wingreen's lab at Princeton University, with experimental resources and training provided by Dr. Bonnie Bassler at Princeton University.