Modeling Min-protein oscillations in bacteria

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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.