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There are two major research projects in the Turnbough laboratory. The first project is to determine the structure and function of the exosporium of Bacillus anthracis spores, the causative agents of anthrax. The exosporium, the outermost permeability barrier of the spore, is a bipartite structure consisting of a paracrystalline basal layer and an external hair-like nap. The filaments of the nap are formed by trimers of the collagen-like glycoprotein BclA. Recent studies suggest that BclA plays a key role in pathogenesis by promoting spore uptake by host professional phagocytic cells that carry the spores to internal tissues where spore germination and bacterial cell growth can occur. The basal layer of the exosporium contains approximately 20 different proteins, including at least three enzymes that play key roles in spore development and virulence. Most basal layer proteins are structural elements that undergo posttranslational modifications necessary for stable exosporium assembly. These modifications, as well as posttranslational modifications of BclA, are currently being actively studied in Dr. Turnbough's lab.
The second project focuses on mechanisms of gene regulation in bacteria—primarily 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 Dr. Turnbough's lab have described control mechanisms in which reiterative transcription during initiation and/or start site switching regulate(s) the expression of several operons involved in pyrimidine biosynthesis and salvage. Recently, he 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.