The PNW RCE Proteomics, Metabolomics, and Lipidomics (PML) Core provides the resources required for the parallel application of proteomic, metabolomic, and lipidomic analyses to diverse sample sets provide by the RCE collaborators. The integration of data generated by these PML Core approaches with the genomic analyses performed by individual Projects and sub-projects (Project 3 (P01) Dr. Michael Katze, Project 4 (P01) Dr. Michael Gale, and Project 5 (R01) Dr. Fred Heffron), creates a unique opportunity to model disease-related pathways (see Biostatistics and Bioinformatics Core) associated with infection by severe acute respiratory syndrome (SARS) virus, flu virus, Ebola virus, West Nile virus (WNV), Dengue virus (DENV), and Francisella novidica. The PML Core will leverage ongoing technical advances in proteomics (including phosphoproteomics), metabolomics, lipidomics, and informatics resources available at PNNL to generate unique suites of systems biology data by performing high throughput, sensitive, and reproducible protein, metabolite, and lipid abundance measurements on comparative and longitudinal samples for iterative cycles of computational modeling and experimental validation. The PML Core provides both resources and support through multiple stages of proteomics, metabolomics, and lipidomics data acquisition, from construction/augmentation of reference accurate mass and time tag (AMT) tag databases through comparative quantitative analyses. Peptide and lipid coverage in AMT tag databases will be enhanced by advanced liquid chromatography separation methods pioneered at PNNL to reduce sample complexity. In the RCE the PML Core will leverage established and ongoing technological advancements at PNNL accomplished under other support in order to perform the large-scale measurements demanded by the Center collaborations.
The application of proteomics, metabolomics, and lipidomics to the study of diseases will aid modeling efforts to elucidate the disease-related pathways associated with infection and has direct relevance in improving the health and potential clinical treatments for infected individuals. Such studies will allow a better understanding of both the natural course of diseases and provide diagnostic and therapeutic targets for the diseases.
|Smithey, Megan J; Venturi, Vanessa; Davenport, Miles P et al. (2018) Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection. Proc Natl Acad Sci U S A 115:E6817-E6825|
|Maurizio, Paul L; Ferris, Martin T; Keele, Gregory R et al. (2018) Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice. G3 (Bethesda) 8:427-445|
|Uhrlaub, Jennifer L; Smithey, Megan J; Nikolich-Žugich, Janko (2017) Cutting Edge: The Aging Immune System Reveals the Biological Impact of Direct Antigen Presentation on CD8 T Cell Responses. J Immunol 199:403-407|
|Pryke, Kara M; Abraham, Jinu; Sali, Tina M et al. (2017) A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses. MBio 8:|
|Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon K (2015) plethy: management of whole body plethysmography data in R. BMC Bioinformatics 16:134|
|Gralinski, Lisa E; Ferris, Martin T; Aylor, David L et al. (2015) Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross. PLoS Genet 11:e1005504|
|Okumura, Atsushi; Rasmussen, Angela L; Halfmann, Peter et al. (2015) Suppressor of Cytokine Signaling 3 Is an Inducible Host Factor That Regulates Virus Egress during Ebola Virus Infection. J Virol 89:10399-406|
|LaBeaud, A Desiree; Banda, Tamara; Brichard, Julie et al. (2015) High rates of o'nyong nyong and Chikungunya virus transmission in coastal Kenya. PLoS Negl Trop Dis 9:e0003436|
|Mirrashidi, Kathleen M; Elwell, Cherilyn A; Verschueren, Erik et al. (2015) Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection. Cell Host Microbe 18:109-21|
|Davis, Zoe H; Verschueren, Erik; Jang, Gwendolyn M et al. (2015) Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Mol Cell 57:349-60|
Showing the most recent 10 out of 127 publications