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

周质外膜蛋白质分选的整体模型

• 批准号: 1412108
• 负责人: Karen Fleming
• 金额: $ 131.78万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1412108&HistoricalAwards=false
• 关键词: Towards; Holistic; Model; Outer; Membrane

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.

该项目将采用数学建模和实验相结合的方法，以开发一个综合的，整体的观点，将蛋白质分选到细菌膜中的基本过程。这项研究将导致对生活在土壤，水中和动物细胞表面的细菌如何生长和成熟的新见解。PI将参与K-12学生的推广，并为研究生和本科生提供培训，他们将参与研究项目，并有机会在国家科学会议上展示他们的工作。杆菌该项目将开发一个全球数学模型，该模型使用常微分方程来描述革兰氏阴性细菌中的外膜蛋白伴侣相互作用和膜蛋白成熟。该模型将进行测试和优化的实验数据的相互作用动力学和热力学的所有成对的相互作用。通过这种方式，整体的数学描述将完全基于严格的实验数据。该项目的一个主要目标是确定是否存在将外膜蛋白分选成外膜的平行途径。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和分子生物物理集群以及物理学部的生命系统物理计划共同支持。