Molecular Mechanisms of Non-coding Bacterial Small RNAs in a Model Quorum Sensing System

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Intellectual Merit: The overall goal of this research is to understand the role of non-coding small RNAs (sRNAs) in controlling cellular processes in bacteria including survival in the environment. The bacterium, Vibrio cholerae, uses cell-cell communication, or quorum sensing (QS), to synchronously regulate expression of four Qrr RNAs (quorum regulatory RNAs) in response to the density of the bacterial population. Recent studies demonstrated that the Qrr sRNAs, like other bacterial sRNAs, can regulate multiple target genes. Although V. cholerae is a transient human pathogen, it is a common inhabitant of the aquatic estuarine and marine ecosystems. This research project is designed to exploit the understanding of the model V. cholerae QS system to discover the role of the Qrr sRNAs in influencing microbial behaviors in diverse environmental settings. Specifically, this project will address the following aims. Aim 1: To identify genes controlled by the quorum sensing-regulated sRNAs. Aim 2: To define the molecular mechanism of sRNA regulation using genetic, biochemical, and computational methods. Aim 3: To assess the conservation of QS circuitry and function in V. cholerae strains isolated from diverse locations. Because sRNAs are involved in important biological functions in all domains of life, defining the mechanism by which these sRNAs act will have fundamental implications for understanding regulatory circuitry of all cellular systems. Moreover, bacterial cell-cell communication systems are widespread in environmentally, commercially, and clinically significant microbes. An understanding of how these signaling pathways function, and how they control bacterial survival in the environment can ultimately engender strategies to curtail world-wide problems of environmental, human, animal and plant health. Broader Impacts: The applicant engages in teaching and service activities aimed at disseminating modern scientific discovery and fostering interactions between members of the academic community and broader society. Training of students includes teaching an undergraduate lecture course and a course for upper level undergraduate Biology majors and graduate students in Prokaryotic Molecular Genetics. Collaborations initiated with researchers within the United States and in India promote international scientific and cultural exchange. Dr. Hammer has also developed an outreach program to engage ethnically diverse urban K-12 students in stimulating hands-on scientific activities that will be shared with local educators who teach under-represented minority students in the metro-Atlanta area. He is a volunteer for science outreach events at Georgia Tech and in the surrounding community, an ad hoc reviewer for multiple journals. He is an active teacher and mentor currently of three undergraduate and two graduate students, and one postdoctoral researcher.