The long term objective of this proposal is to determine the molecular processes involved in the regulation and mechanism of cell division in E. coli. Our efforts have focused on a cluster of cell division genes, especially the first gene which plays a key role in the division process. Recent studies have suggested that ftsZ acts earliest in the division pathway, is rate-limiting for cell division and is the target of two inhibitors of cell division, SulA, a component of the SOS response, and MinCD, a part of the min system that is involved in the proper localization of the division site. More recently, our immunolocalization studies have shown that FtsZ is specifically located near the cytoplasmic membrane at the leading edge of the division septum. The FtsZ appears in a ringlike structure that contracts during the division process. In our model for cell division we propose that FtsZ self assembles at the division site and acts as a cytoskeletal element to activate and coordinate the division process. The present proposal is aimed at further exploring FtsZ localization. We wish to confirm that FtsZ localizes before there is a visible invagination. Other experiments are aimed at determining if the inhibitors of division, SulA and MinCD, block Z-ring formation or function. Also, we will determine if a block to division imposed by various fts mutations block Z-ring development. The role of FtsZ in cell division will be explored by characterization of the purified protein. Experiments are aimed at examining its ability to self assemble and its interaction with various nucleotides. In addition, biochemical and genetic experiments are aimed at determining what proteins FtsZ interacts with. Candidate proteins are FtsA and SulA. Also, genetic experiments are aimed at identifying regulatory components that contribute to the major ftsZ promoters. Our work has shown that ftsZ is highly conserved among the eubacteria and is essential for vegetative and sporulation division in the Gram positive bacterium B. subtilis. Therefore, this protein could be a potential useful target for antimicrobial agents.
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