Modeling Min-protein oscillations in bacteria

描述(申请人提供)：这项研究的长期目标是探索最小蛋白振荡在细菌细胞分裂中所起的作用。这项建议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(COCCI)(如淋球菌)中振荡的定量模型。对Min蛋白的建模和实验的耦合将有助于回答两个基本问题：(1)Min蛋白振荡如何有助于大肠杆菌和相关细菌中细胞分裂的可靠性和极端准确性？(2)Min蛋白振荡是否能够选择近圆形球菌中细胞的最长轴来定义分裂平面？为了从理论上解决第一个问题，我们将开发一个粒子级别的模拟最小蛋白在大肠杆菌中的振荡。该模拟将跟踪数千个个体思维和矿物质蛋白质(颗粒)在三维(3D)细胞几何中的扩散和相互作用。模拟将建立在现有模型的基础上，这些模型考虑的是蛋白质密度，而不是单个蛋白质分子。粒子水平的模拟将首次捕捉到Min系统的几个实验观察到的特征，包括与膜相关的Mind聚合物的螺旋组装和振荡图案的显著随机波动。为了补充和扩展我们的建模结果，我们将合作通过将振荡周期、内侧分裂的准确性和极分裂的开始(微型天花板)相关联来实验定义Min系统的作用是细胞分裂的准确性。为了解决第二个问题，我们将把Min-Protein模拟扩展到Cocci。为了确定Min-Protein振荡是否能够选择近圆形细胞的最长轴，将对一系列大小和形状的细胞进行粒子级模拟。这些模拟的结果，加上淋球菌Min振荡的成像实验，将确定Min系统在确定球菌的分裂平面方面的可能作用。对上述问题的回答将有助于理解细胞如何识别自己的形状--这是一个对细胞分裂、细胞运动以及在原核生物和真核生物中创建多细胞结构的重要问题。

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.