Lab Research Focus
Currently, there are three major research projects in my laboratory. The first project is to identify and determine the function of the components of the exosporium of spores of Bacillus anthracis, the causative agent of anthrax. The exosporium, the outermost layer of the spore, is composed of polysaccharides, lipids, and ~20 different proteins. It is the primary site for spore interactions with the environment and host defenses and presumably plays major roles in spore survival and pathogenesis. The ultimate goal of this project is to identify macromolecular factors on the surface of the B. anthracis spore that are potential targets for new vaccines and drug intervention for the prevention and treatment of anthrax. The second project is to discover ligands that can be used to capture and detect B. anthracis spores. We are focusing on two types of ligands – short peptides and monoclonal antibodies (mAbs). Using phage displayed peptide libraries, we have identified ~7 amino acid-long peptides that bind tightly and species-specifically to B. anthracis spores. We are also characterizing the spore receptors/antigens to which the peptide ligands/mAbs bind. The third project focuses on mechanisms of gene regulation in Escherichia coli that involve reiterative transcription and/or transcriptional start site switching. Reiterative transcription is the repetitive addition of a nucleotide to the 3’ end of a nascent transcript due to slippage between the transcript and DNA template. Start site switching is the selection of alternative start sites at a single promoter, which results in the synthesis of transcripts with different potentials for translation. Previous studies in our lab have described control mechanisms in which reiterative transcription during initiation and/or start site switching regulates the expression of several operons involved in pyrimidine biosynthesis and salvage. Recently, we discovered additional operons that appear to use reiterative transcription and/or start site switching to regulate their expression by mechanisms unlike those previously described. These new mechanisms are presently being elucidated. In addition, studies are in progress to define the mechanisms of reiterative transcription and start site switching and the factors that modulate the extent of these reactions.
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