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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-EC-M)
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Icahn School of Medicine at Mount Sinai
New York
United States
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Pohl, Marie O; von Recum-Knepper, Jessica; Rodriguez-Frandsen, Ariel et al. (2017) Identification of Polo-like kinases as potential novel drug targets for influenza A virus. Sci Rep 7:8629
Hartmann, Boris M; Albrecht, Randy A; Zaslavsky, Elena et al. (2017) Pandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic cell death. Nat Commun 8:1931
Lobingier, Braden T; Hüttenhain, Ruth; Eichel, Kelsie et al. (2017) An Approach to Spatiotemporally Resolve Protein Interaction Networks in Living Cells. Cell 169:350-360.e12
Rialdi, Alexander; Hultquist, Judd; Jimenez-Morales, David et al. (2017) The RNA Exosome Syncs IAV-RNAPII Transcription to Promote Viral Ribogenesis and Infectivity. Cell 169:679-692.e14
Soonthornvacharin, Stephen; Rodriguez-Frandsen, Ariel; Zhou, Yingyao et al. (2017) Systems-based analysis of RIG-I-dependent signalling identifies KHSRP as an inhibitor of RIG-I receptor activation. Nat Microbiol 2:17022
García-Sastre, Adolfo (2017) Ten Strategies of Interferon Evasion by Viruses. Cell Host Microbe 22:176-184
Martín-Vicente, María; Medrano, Luz M; Resino, Salvador et al. (2017) TRIM25 in the Regulation of the Antiviral Innate Immunity. Front Immunol 8:1187
Patzina, Corinna; Botting, Catherine H; García-Sastre, Adolfo et al. (2017) Human interactome of the influenza B virus NS1 protein. J Gen Virol 98:2267-2273
Park, Ryan J; Wang, Tim; Koundakjian, Dylan et al. (2017) A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors. Nat Genet 49:193-203
Schotsaert, Michael; García-Sastre, Adolfo (2017) Inactivated influenza virus vaccines: the future of TIV and QIV. Curr Opin Virol 23:102-106

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