Modeling Min-protein oscillations in bacteria

描述（由申请人提供）：本研究的长期目标是探索min -蛋白振荡在细菌细胞分裂中的作用。该提案的具体目标是开发和测试Min蛋白在杆状细胞（如大肠杆菌）和圆形细胞（球菌）（如淋病奈瑟菌）中振荡的定量模型。Min蛋白的建模和实验的结合将有助于回答两个基本问题：(1)Min蛋白振荡如何促进大肠杆菌和相关细菌细胞分裂的可靠性和极端准确性？(2)在近圆形的球菌中，Min-protein振荡是否能够选择细胞的最长轴来确定分裂平面？为了从理论上解决第一个问题，我们将开发大肠杆菌中最小蛋白振荡的粒子水平模拟。模拟将遵循在三维（3D）细胞几何结构中数千个个体MinD和MinE蛋白质（粒子）的扩散和相互作用。模拟将建立在考虑蛋白质密度而不是单个蛋白质分子的现有模型上。粒子级模拟将首次捕捉到实验观察到的Min系统的几个特征，包括膜相关MinD聚合物的螺旋组装和振荡模式的显著随机波动。为了补充和扩展我们的建模结果，我们将合作通过实验确定Min系统的作用是通过相关振荡周期，中间分裂的准确性和极性分裂（迷你细胞）的开始来确定细胞分裂的准确性。为了解决第二个问题，我们将把Min-protein模拟扩展到球菌。为了确定Min-protein振荡是否能够选择近圆形细胞的最长轴，粒子级模拟将应用于具有一系列大小和形状的细胞。这些模拟的结果，连同淋病奈瑟菌最小振荡的成像实验，将确定最小系统在确定球菌分裂平面中的可能作用。上述问题的答案将有助于理解细胞如何识别自己的形状——这对原核生物和真核生物的细胞分裂、细胞运动和多细胞结构的形成都是一个重要的问题。

DESCRIPTION (provided by applicant): The long-term aim of this research is to explore the role played by Min-protein oscillations in bacterial cell division. The specific goal of this proposal is to develop and test a quantitative model for oscillations of the Min proteins in both rod-shaped cells such as Escherichia coli and round cells (cocci) such as Neisseria gonorrhoeae. The coupling of modeling and experiment for the Min proteins will help answer 2 fundamental questions: (1) How do Min-protein oscillations contribute to the reliability and extreme accuracy of cell division in E. coli and related bacteria? (2) Are Min-protein oscillations able to select-the longest axis of the cell in nearly round cocci in order to define the division plane? To address the first question theoretically, we will develop a particle-level simulation of Min-protein oscillations in E. coli. The simulation will follow the diffusion and interactions of thousands of individual MinD and MinE proteins (the particles) in a three-dimensional (3D) cell geometry. The simulation will build on existing models that consider protein densities rather than individual protein molecules. The particle-level simulation will capture several experimentally observed features of the Min system for the first time, including the helical assemblage of membrane-associated MinD polymers and the significant stochastic fluctuations of the oscillation pattern. To complement and extend our modeling results, we will collaborate to experimentally define the role of the Min system is cell-division accuracy by correlating oscillation period, the accuracy of medial divisions, and the onset of polar divisions (mini celling). To address the second question, we will extend the Min-protein simulations to cocci. To determine whether Min-protein oscillations are able to select the longest axis of nearly round cells, particle-level simulation will be applied to cells with a range of sizes and shapes. The results of these simulations, together with imaging experiments of Min oscillations in N. gonorrhoeae, will define a possible role for the Min system in determining the division plane in cocci. Answers to the above questions will contribute to an understanding of how cells recognize their own shape - an issue of importance for cell division, cell motility, and the creation of multicellular structures in both prokaryotes and eukaryotes.