Probing the molecular interactions and architecture of bacterial cell division proteins

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Cellular microbiology has seen a renaissance in the past several years, spurred in part by advances in imaging techniques. Our ability to peer into cells to see the localization and organization of macromolecular complexes involved in fundamental processes has advanced our understanding of how bacteria move, associate and divide. In gram-negative bacteria, a group of proteins known as the divisome drives the synchronized invagination of the inner and outer membranes and peptidoglycan synthesis at the newly formed septum. Divisome proteins form the multicomponent Z-ring structure, which is primarily composed of the tubulin homologue FtsZ. The dynamics of FtsZ filament formation are considered essential for proper Z-ring assembly. In Escherichia coli, ~10 essential and over 20 nonessential proteins are involved in divisome assembly. Interactions occur in a hierarchical manner, and the proposed mechanisms of cell division can be divided into three distinct stages - early, intermediate and late. Although bacterial cell division has been intensively studied at the cellular and molecular levels for decades, with many of the key protein players identified, critical questions remain about the molecular mechanisms and protein interactions that govern the formation and dynamics of the divisome. ***This research program aims to elucidate the protein interactions and macromolecular structures involved in Z-ring stability and dynamics. Specifically, we will identify and characterize the interactions and macromolecular architecture of FtsZ and the Zap family of proteins. These interactions are critical for early-stage cell division, and the overlapping functions of the Zap proteins have been implicated in Z-ring-mediated septation. We will also determine the protein interactions in intermediate-stage cell division that govern how FtsK, an essential cell division `checkpoint' protein, links division of the cytoplasm with septation and cell wall invagination. We will address these questions using an original combination of biochemical, molecular and cutting-edge imaging tools, which will lead to groundbreaking advances in cell division. The long-term vision for this research program is to develop a complete biochemical and structural picture of bacterial cell division during all of its distinct stages, thereby elucidating the mechanisms that drive this essential process. Our findings and the approaches we develop will transcend prokaryotic cell biology and will be applicable to diverse biological systems.**