Towards a Holistic Model for Outer Membrane Protein Sorting in the Periplasm

该项目将采用数学建模和实验相结合的方法，对细菌膜中蛋白质分类的基本过程进行综合、全面的研究。这项研究将对生活在土壤、水和动物细胞表面的细菌如何生长和成熟产生新的见解。PI将与K-12学生接触，并为研究生和本科生提供培训，这些学生将参与研究项目，并有机会在国家科学会议上展示他们的工作。该项目的长期目标是对膜蛋白通过外周质进入大肠杆菌外膜的通量进行定量描述。该项目将开发一个全球数学模型，使用常微分方程来描述革兰氏阴性细菌的外膜蛋白伴侣相互作用和膜蛋白成熟。该模型将通过所有成对相互作用的相互作用动力学和热力学实验数据进行测试和优化。这样，整体的数学描述将完全以严格的实验数据为基础。该项目的一个主要目标是确定是否存在将外膜蛋白分选到外膜的平行途径。该奖项由分子和细胞生物科学部的细胞动力学和功能集群、分子生物物理学集群以及物理部的生命系统物理学项目共同支持。

This project will employ a combination of mathematical modeling and experimentation to develop an integrated, holistic view of the essential process of sorting proteins into membranes in bacteria. This research will lead to novel insights into how bacteria, which live in soil, water, and on the surfaces of animal cells, grow and mature. The PI will engage in outreach to K-12 students, and provide training to graduate and undergraduate students who will participate in the research project and have the opportunity to present their work at national scientific meetings.The long-term goal of this project is to develop a quantitative description of the flux of membrane proteins through the periplasm and into the outer membranes of E. coli. The project will develop a global mathematical model that uses ordinary differential equations to describe outer membrane protein chaperone interactions and membrane protein maturation in gram-negative bacteria. The model will be tested and optimized by experimental data on the interaction kinetics and thermodynamics of all pairwise interactions. In this manner, the holistic mathematical description will stay fully grounded by rigorous experimental data. A major goal of the project is to determine whether or not parallel pathways exist for the sorting of outer membrane proteins into outer membranes.This award is jointly supported by the Cellular Dynamics and Function Cluster and the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences, and by the Physics of Living Systems Program in the Division of Physics.