EXCEED THE SPACEPROVIDED.Microbes responsible for infectious disease outbreaks - from either natural, e.g., multidrug-resistantStaphylococcus aureus, or bioterrorism, e.g.,anthrax, causes - are typically virulent forms of a singlespecies. Population genomics, which is the study of intraspecific variations of a single microbial species, istherefore a key to uncovering virulence factors and disease-causing mechanisms, as well as tracking thesources of microbial disease. The Evolutionary Informatics Lab at Hunter College is a vital partner in a multi-institutional team of comparative genomics of Borrelia burgdorferi, the Lyme disease agent. We areresponsible for the bioinformatics system development and evolutionary statistical analysis, includingexperimental design, data processing and warehousing, and evolutionary analysis. Through evolutionarystatistical analysis our lab discovered a surprisingly high amount of genetic exchange and plasmid transfer inB. burgdorferi. To continue our success in characterizing the population structure of pathogenic bacteriabased on comparative genomics, I propose a 5-years project to develop a bioinformatics infrastructurededicated to the analysis of population variations of pathogenic microbes. We have two specific aims in thisproposal. First, we will develop a novel statistical framework - non-housekeeping multilocus sequencingtyping (NH-MLST) - of analyzing the bacterial intraspecific variations in a phylogenetic context, with the goalof detecting genes responsible for adaptive evolution in bacteria. Second, we will develop a computationalinfrastructure dedicated to the comparative genomics of closely related bacteria. As comparative microbialsequencing becomes a standard approach for discovering virulence factors and tracing microbial outbreaks,the proposed project will provide a robust evolutionary analytical framework and an efficient computationalsystem for comparative microbial genomics.
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