Hammer, Brian K.
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ItemEavesdropping on the conversations of an environmental pathogen(Georgia Institute of Technology, 2009-09-11) Hammer, Brian K. ; Parker H. Petit Institute for Bioengineering and Bioscience ; Georgia Institute of Technology. School of BiologyThe overall goal of the research in the Hammer lab is to understand the role of non-coding small RNAs (sRNAs) in controlling cellular processes in bacteria. sRNAs are ubiquitous regulators in bacteria, plants and animals. By base pairing directly with an mRNA, a sRNA alters the fate of the mRNA, the level of target protein made, and in turn, behaviors controlled by that protein. Bacteria encode ~100 sRNAs, and the few studied in detail control multiple target mRNAs. Thus, understanding the significance that sRNAs play in regulating cellular processes requires target identification, and definition of the molecular mechanisms governing the sRNA/mRNA base pairing interactions. The focus of this research is on Vibrio cholerae, which uses a process of cell-cell communication, called quorum sensing (QS), to synchronously regulate expression of four Qrr sRNAs (quorum regulatory RNAs) in response to the population density of the bacteria. The only target of the Qrr sRNAs was originally believed to be the mRNA encoding a regulatory protein, HapR, which has garnered the majority of attention in V. cholerae QS research because it regulates a virulence pathway. However, I recently discovered that the Qrr sRNAs, like other bacterial sRNAs, regulate additional target genes distinct from the HapR-controlled virulence pathway. V. cholerae is a common marine inhabitant, and only a transient human pathogen, therefore, the research in this proposal is designed to exploit our understanding of the V. cholerae QS paradigm for the identification of novel sRNA target genes, and to dissect the role that QS and the Qrr sRNAs play in behaviors distinct from virulence.
ItemSmall RNA Regulation of the Quorum Sensing Response in the Bacterial Pathogen Vibrio Cholerae(Georgia Institute of Technology, 2011-06-14) Hammer, Brian K. ; Parker H. Petit Institute for Bioengineering and Bioscience ; Georgia Institute of Technology. School of BiologyVibrio cholerae, the waterborne bacterium responsible for the deadly disease cholera, is both a transient human pathogen and a ubiquitous inhabitant of marine environments. The pathogenesis and ecology of this deadly microbe are the focus of research in the Hammer lab. V. cholerae has become a model organism to understand a process of microbial cell-cell communication called quorum sensing, which allows bacterial groups to act in unison by synchronizing gene expression in response to population density. V. cholerae, and many other Vibrio species, achieves quorum sensing by producing and then responding to chemical signal molecules, called autoinducers, which control the production of multiple regulatory small RNAs. In V. cholerae, these non-coding sRNAs are predicted to base-pair with, and alter the translation of, several mRNAs encoding protein regulators that alter the expression of >100 genes. Many of the quorum-sensing regulated genes (such as the cholera toxin and attachment factors) are critical for host colonization, while others (such as genes involved in horizontal gene transfer) are important in marine ecosystems. We are currently using genetic, biochemical, and computational methods to define the mechanism of sRNA control and the role of V. cholerae quorum sensing in clinical and environmental settings.