Molecular mechanisms of bacterial cell division

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Cell division is one of the most fundamental processes in biology. Bacterial cells divide through the coordinated action of multiple protein systems that replicate genes, expand cellular envelopes, and partition cells to give rise to progeny. The collection of cell division proteins is commonly known as the divisome. In Gram-negative bacteria, the divisome drives the synchronized invagination of the inner- and outer-membranes along with peptidoglycan (PG) synthesis at the newly formed septum. To achieve this, divisome proteins form a multicomponent ring-like structure at the site of cell division. In Escherichia coli, ~10 essential and over 20 nonessential proteins are involved in divisome assembly. The protein interactions occur in a hierarchical manner, starting with the cell division protein FtsZ, a bacterial tubulin homolog. Polymerization of FtsZ at midcell forms a cytoskeletal scaffold known as the Z ring. FtsA and ZipA tether the Z ring to the inner membrane, while a series of FtsZ associated proteins, ZapA to D, subsequently localize at the cell division site independently of each other and likely act to stabilize and organize the Z ring. Next, several integral membrane proteins, FtsK, FtsQ, FtsL/FtsB, FtsW, FtsI, and FtsN, are sequentially recruited to the Z ring. FtsI, FtsW, and FtsN are required for septal PG synthesis, while the FtsQ/FtsL/FtsB heterocomplex and FtsK may connect the Z ring to the proteins involved in PG synthesis. Bacterial cell division has been intensively studied at the cellular and molecular levels for decades and many of the key protein players have been identified. However, critical questions remain about the molecular mechanisms and protein interactions that govern the formation and action of the cell division machinery. The objectives of this research program are built directly on my previous NSERC Discovery Grant. We will use multidisciplinary and complementary approaches to reveal important aspects of protein-protein interactions that drive the formation of the bacterial divisome and the mechanism of bacterial cell division. This research program will give HQP the opportunity to engage in cutting-edge scientific endeavors, with an explicit emphasis on problem solving and collaboration building. Combined with guidance and encouragement, these opportunities will lead to high-impact publications and the development of imaginative, independent scientists who will be well prepared for careers in Canadian academia, government and industry.