Mechanisms of membrane biogenesis and peptidoglycan remodeling during sporulation

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My research program seeks to understand the structural and functional changes that occur in the bacterial cell envelope during growth and cell division. Although bacteria occupy every niche in the biosphere and sustain life on this planet, they are faced with unpredictable environments. To survive, they have evolved a sophisticated, multilayered cell envelope structure composed of either one or two membranes and a mesh-like polymer (peptidoglycan) that protects them while allowing the selective passage of nutrients and waste products. Spatial and temporal regulation of changes in the cell envelope is essential to bacterial growth and division. Moreover, the bacterial cell envelope is a major target for antimicrobials. Thus, research into the bacterial cell envelope provides insight into fundamental biological processes and is critical for understanding human health and disease. Some bacteria have evolved mechanisms to protect their DNA from harsh environmental conditions by forming spores. These spores can remain viable for years without water or nutrients and can resist UV irradiation, heat, pH extremes and oxidative damage. Spore formation involves complex morphological changes in the membranes and peptidoglycan of single- and double-membraned bacteria and thus is ideal for studies of the bacterial cell envelope. In addition to being a useful model system, spore formation has significant implications for human health and disease. Examples of sporulating pathogenic bacteria include Bacillus cereus, which causes foodborne illness, Clostridium botulinum and C. tetani, the causative agents of botulism and tetanus, respectively, and Bacillus anthracis, which has been linked to bio-terrorism. Sporulating bacteria have been used for the production of antibiotics and enzymes, the delivery of vaccines and therapeutic agents, and the design of whole-cell biosensors. Interfering with the formation of a mature spore can help further develop better antimicrobial agents. By applying a range of approaches drawn from bioinformatics, molecular genetics, cell biology and structural biology with main emphasis on cryo electron tomography and super-resolution fluorescence light microscopy, I will characterize the structural and functional changes of the bacterial cell envelope during sporulation. Over the next five years, my research program will focus on characterizing two aspects of sporulation: 1) biogenesis of the outer membrane in double-membraned bacteria and 2) peptidoglycan remodeling in single- and double-membraned bacteria.