Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized periodontopathogen. Although this pathogen mainly inhabits periodontal pockets it also is present in other niches of the oral cavity enroute to the periodontal pockets such as tongue as well as it can access distant parts of body such as cardiovascular system and heart tissues. Finally, it also can invade and survive within host cells. In order to adapt to the various niches the organism is expected to have efficient regulatory mechanisms allowing it to rapidly alter gene and ultimately protein expression in response to the various challenges imposed by the various host environments. Two global regulatory proteins OxyR and RprY have recently been reported. However, recent reports show that small non-coding RNAs (sncRNAs) have a role in regulation of various critical functions in several bacteria as well as in other organisms. So far, however, the role of sncRNAs in P. gingivalis and other anaerobic bacteria has not been investigated. It is noteworthy that, analysis of the genomic sequence of P. gingivalis W83 predicted the presence of as many as 650 sncRNAs. Empowered by the availability of the data as well as inspired by the large number of the predicted small sncRNAs in this organism we propose to start dissecting the role of the RNAs in this organism. Thus, first we will experimentally verify the presence of these RNAs in P. gingivalis W83 variety of techniques. We then will define the role in gene regulation as well as targets of four selected sncRNAs. We expect that once completed this work will identify majority of sncRNAs in P. gingivalis as well as set the stage for further elucidation of mechanisms of regulation by the RNAs in this bacterium. Finally, since these RNAs maybe conserved among related organisms we predict that this work will shed light on the mechanisms of sncRNA-mediated regulation in other Bacteroides-related bacteria such as Prevotella intermedia, Tannerella forsythensis, Bacteroides fragilis, B. thetaiotaomicron and Capnocytophaga hutchinsonii. PUBLIC HEALTH RELEVANCE: The long-term objective of this application is to identify and characterize the regulatory mechanisms mediated by small RNAs encoded on the genomes of anaerobic bacteria. Oral periodontal pathogens have to respond to constantly changing environmental conditions, however, so far the regulatory mechanisms governing the gene expression are poorly understood. Our work is expected to provide clues how the bacterium tolerates various environments and ultimately, we predict that this work will lead to identification of targets for the design of novel and specific therapeutic agents for treatment of periodontal diseases.