Protein-protein interactions and assembly in the cell
In my lab, the broad goal is to understand the mechanisms and cellular control of protein-protein assembly processes and to study general principles governing protein-protein interactions in the cell. Our approach combines theory, model building, and computer simulation to:
1. Develop new methods to model the dynamics of protein interactions in a rigorous theoretical framework
Many challenges exist in simulating cell-scale dimensions while retaining accuracy in describing the physics of protein association. We develop accurate methods for single particle reaction-diffusion using controlled approximations.
2. Use coarse-grained models to investigate general principles governing networks of protein association in the cell
Protein-protein interaction networks specify which proteins bind to one another in the cell to perform their biological function. However, they do not adequately capture the competition between proteins to bind to shared partners and the cooperation between proteins to form multi-protein complexes. These details on protein binding interfaces as well as protein concentrations are critical to understand how proteins dynamically interact with one another in the cell and avoid forming spurious, nonfunctional and potentially disease causing associations. We investigate how the structure of the network and the availability of proteins contributes to their binding specificity and functional evolution.
3. Apply modeling strategies to specific assembly processes in the cell to determine mechanisms of timing and control
Many processes, including protein coat formation and tubulin growth, require the collective participation of many proteins. In clathrin-mediated endocytosis, a pathway used by all eukaryotes for internalizing cargo and nutrients, the early stages of membrane vesicle formation requires the formation of a clathrin protein coat on the plasma membrane. This protein coat formation proceeds through the cooperation of dozens of different protein types. We are interested in understanding how the timing and frequency of processes such as protein coat formation are controlled and regulated by the cell.