Eavesdropping on the conversations of an environmental pathogen
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The 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.
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