The overall goal ofthe Modeling Core is to drive the integration of global -OMICS data to identify virus-host networks that control the innate immune response and influence pathogenicity. This will be accomplished through two main objectives a) to design and provide tools to analyze -OMICS data and b) to serve as an engine for integrating -OMICS data into network models of pathogenicity that are subject to further refinement in an iterative fashion. This Core will employ existing bioinformatics and systems biology approaches as well as develop novel approaches to identify cellular proteins and networks which influence influenza virus replication and contribute to virulence in vivo. The modeling core will be the engine for translating -OMICS data into biological insight and has a central role in the successful completion of this program. Co-directors Bandyopadhyay and Krogan have a strong history of innovation and collaboration with each other and others on this proposal and are well suited to direct the modeling efforts. Predictions that are based upon our models will be tested in primary cell culture and in animal model systems by employing targeted -OMICS technologies as well as in vivo experimentation and analysis of clinical phenotypes.
Innate signaling pathways can regulate influenza replication, but there remain critical gaps in our knowledge about how these responses impact viral disease pathogenesis. The modeling core aims to define the cellular networks involved in pathogenic infection and use this information to identify inhibitors (small molecules, blocking antibodies) which can block pathogenesis and human mutations which predispose to infection.
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