The Proteomics, Metabolomics, and Lipidomics Core will be located at Pacific Northwest National Laboratory (PNNL). PNNL OMICs Core measurements will be based upon world-class mass spectrometry (MS)-based platforms and the availability of unique capabilities and resources. Ultra-sensitive proteomics analyses will be performed using the accurate mass and time (AMT) tag approach together with high resolution mass spectrometry, a process that offers high OMIC coverage, high quantitative precision, and high sensitivity with small sample-size requirements. Quantification of global phosphopeptide measurements will be obtained using ITRAQ stable isotope labeling. The global metabolomics and lipidomics components of this Core will utilize GC-MS and LC-MS, respectively. These studies will enhance our understanding of the host response to infection by evaluating changes in the abundance for the broad range of host proteins, metabolites, and lipid molecules that directly carry out biological functions. Based on the results of complementary transcriptomics (analyzed in parallel outside of this Core) and global MS-based OMICs data or a priori knowledge of the biological systems under study, we will also then employ multiplexed targeted MS-based analyses for quantifying a defined number of substrates and/or products of corresponding encoded proteins. These targeted proteomics, metabolomics and lipidomics analyses will provide accurate absolute quantification based on stable-isotope dilution where feasible

Public Health Relevance

The broad molecular profiles for influenza, Ebola, and West Nile viral infection generated by this OMICs Core and provided to the Computational Modeling Core is expected to enable under this Program new mechanistic insights into host-pathogen interactions and thereby aid in our ability to combat global health concerns attributed to these viral infections.

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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University of Wisconsin Madison
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Thackray, Larissa B; Shrestha, Bimmi; Richner, Justin M et al. (2014) Interferon regulatory factor 5-dependent immune responses in the draining lymph node protect against West Nile virus infection. J Virol 88:11007-21
Menachery, Vineet D; Eisfeld, Amie J; Schäfer, Alexandra et al. (2014) Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. MBio 5:e01174-14
Diamond, Michael S; Schoggins, John W (2013) Host restriction factor screening: let the virus do the work. Cell Host Microbe 14:229-31