This application is a re-submission of a revised application in response to two NIH program announcements: PA-98-070, """"""""Research on Microbial Biofilms,' and PA-97-073, 'Mucosal Immunity in Pathogenesis/Prevention of Human Disease."""""""" The goal of the proposed work is to use otorrhea as a model system to increase understanding of the interplay between the host mucosa and a community of bacteria termed a mucosal biofilm. The investigators argue that a complete understanding of this interplay can only be gained by comprehensively evaluating the gene expression patterns (expressomes) of both organisms simultaneously. Advances in gene expression detection technology have been made possible by the convergence of three technologies: 1. Advancements in robotic instrumentation for the preparation of arrayed, addressable libraries, 2. Automated imaging technology for simultaneously comparing the expression levels of thousands of genes, 3. and Programs which permit visualization of huge amounts of data in an easily understood format. The investigators hypothesize that Pseudomonas aeruginosa (PA) biofilms play an important role in acute otorrhea and chronic suppurative otitis media (CSOM) and that the expressomes of the pathogen and host undergo progressive changes during the establishment of an infection. The investigators also theorize that mucosal biofilms interact with """"""""implant"""""""" PA biofilms that form on tympanostomy tubes causing changes in species composition, and that biofilm-resistant ventilation tubes may be effective in reducing post-tympanostomy otorrhea. The investigators seek to develop a comprehensive picture of the changes and interactions of the expressomes of Ps. aeruginosa and the host mucosa during the development of a biofilm. This will be accomplished using state-of-the-art gene expression technology to characterize specimens obtained from two complementary animal models (the chinchilla model for acute otorrhea and the cynomolgus monkey model for chronic otorrhea). Gene expression changes will be correlated with changes in protein expression and with phenotypic characters. This proposal combines the expertise of three major centers, the Center for Genomic Sciences (which developed the paradigm of otitis as a biofilm disease), the Center for Biofilm Engineering (an NSF Engineering Center), and Children's Hospital of Pittsburgh.
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