Training in Systems Biology for the Study of Host-Pathogen Interactions

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DESCRIPTION (provided by applicant): My long term goal is to better understand the mechanisms used by mucosal epithelial cells to recognize the initiation of infections. The squamous mucosa of the oral cavity and oropharynx and related tissues are of particular interest as primary portals of entry and Interactions with pathogens in a background of commensal organisms. My training goal in this six week program is to learn to apply systems biology concepts analyses to the study of the initiation of infectious diseases. To foster this goal, I will learn to: 1. interrogate Innate DB for protein-interaction networks (PINS) that are modulated by key mutations engineered in a murine model of gastrointestinal infections; and 2. predict hubs of PINs, and validate experimentally. Human health requires that the oral and oropharyngeal portals distinguish commensals from pathogens. Evidence from our lab suggests that mucosal epithelial cells are primary sensors, distinguishing harmful organisms from harmless commensal colonizers. Furthermore, we have shown that oral epithelial cells can be invaded by enteric pathogens like Listeria and Salmonella, yet these bacteria rarely cause infections of the squamous mucosal epithelium. Conversely, oral pathogens like Porphyromonas gingivalis cause local infections of the supporting structures of the teeth, yet are swallowed but fail to cause infection'in the gastrointestinal tract. Innate DB is a program that permit visualization, interrogation and analysis of the complex signaling that occurs In virtually any tissue, including epithelia, based on gene expression and protein production profiles and curated, archived databases of relevant information. By understanding the signaling responses of the oral and oropharyngeal epithelia to the local pathogens and transient enteric pathogens, we can design better preventive therapies against oral and enteric infections.