i. Molecular Mechanisms of Energy-Dependent Proteins during Essential Cell Processes
Energy-dependent molecular machines are proteins that harness chemical energy released upon nucleotide hydrolysis and translate that energy into mechanical work. Molecular machines are involved in every cellular process, such as genetic replication, establishment and maintenance of the proteome, molecular transport, motility, respiration, growth and division. My research is focused on determining how energy-dependent molecular machines accomplish vital tasks, how these tasks influence the compendium of cellular processes, and the interplay between these cellular processes and the components involved.
ii. Cell Division in Bacteria
The cell division pathway is an example of a complex cellular process that requires the contributing activities of many molecular machines. These activities must be precisely coordinated and regulated both spatially and temporally for cells to divide. In bacteria, the process of division, or cytokinesis, entails multiple steps, including assembly of division protein complexes at midcell, membrane constriction, insertion of new cell wall components and separation of daughter cells. Our laboratory is interested in studying the biochemical mechanisms of proteins that modulate the cellular position of the division machinery, referred to as the Min system, as well as the machinery that promotes constriction (FtsZ and FtsZ-interacting proteins).
iii. Regulated Proteolysis
Protein degradation is utilized by the cell to maintain the cellular proteome and promote homeostasis. Regulated proteolysis can be used to control cellular responses to stimuli and modulate cellular processes. The ATP-dependent chaperone protease complex known as ClpXP is a molecular machine that unfolds protein substrates bearing specific recognition tags and degrades them. One substrate degraded by ClpXP in E. coli is the essential protein FtsZ. Our lab is working on how degradation of cell division proteins such as FtsZ modulates the process of cell division in E. coli. This work will not only lead to a better understanding of the fundamental process of cell division, but will also lead to a better understanding of the biochemical mechanisms of substrate recognition and protein unfolding by ATP-dependent molecular chaperones and degradation by cognate proteases.