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

Johns Hopkins University, Baltimore MD

Investigators

Abstract

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.