This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A large number of viruses, including many human pathogens (dengue, yellow fever, west nile virus, etc), are transmitted by insects. The long-term goal of this proposal is to examine the mechanism of the antiviral defense system in Drosophila melanogaster. RNA interference (RNAi) is an ancient and conserved nucleic acid-based immune system in insects. Accordingly, insect viruses evolved strategies to control this defense mechanism. For example, Cricket Paralysis Virus (a Dicistrovirus) encodes a protein that suppresses RNAi by interacting specifically with the endonuclease Ago2. In more general terms, our understanding of the interactions of RNA viruses with the invertebrate hosts is very limited nevertheless requires urgent attention. The outcome of virus infection is the result of multidimensional set interactions of virus and host factors. Indeed, many viral and host proteins function as a complex than acting as a single molecule to regulate a vast number of cellular processes. Chemical crosslinking mass spectrometry of purified complexes derived from virus infected cells is a useful technique for mapping the site of linkage between two interacting partners in a complex and provides valuable information on three dimensional functional architecture of the protein complex. In addition, post translational modification events (e.g. phosporylation) of cellular signaling pathways are critical to regulate the antiviral mechanisms and often takes place upon infection that leads to change in cellular protein expression. The present research plan is designed to address how RNA viruses particularly Dicistroviruses interacts with host machinery to their advantage using Drosophila as a model organism and crosslinking mass spectrometry and phospoproteomics approaches.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001614-29
Application #
8363841
Study Section
Special Emphasis Panel (ZRG1-BCMB-M (40))
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
29
Fiscal Year
2011
Total Cost
$5,765
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Liu, Tzu-Yu; Huang, Hector H; Wheeler, Diamond et al. (2017) Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics. Cell Syst 4:636-644.e9
Twiss, Jeffery L; Fainzilber, Mike (2016) Neuroproteomics: How Many Angels can be Identified in an Extract from the Head of a Pin? Mol Cell Proteomics 15:341-3
Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Julien, Olivier; Zhuang, Min; Wiita, Arun P et al. (2016) Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proc Natl Acad Sci U S A 113:E2001-10
Bongrand, Clotilde; Koch, Eric J; Moriano-Gutierrez, Silvia et al. (2016) A genomic comparison of 13 symbiotic Vibrio fischeri isolates from the perspective of their host source and colonization behavior. ISME J 10:2907-2917
Cil, Onur; Phuan, Puay-Wah; Lee, Sujin et al. (2016) CFTR activator increases intestinal fluid secretion and normalizes stool output in a mouse model of constipation. Cell Mol Gastroenterol Hepatol 2:317-327
Kintzer, Alexander F; Stroud, Robert M (2016) Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana. Nature 531:258-62
Bradshaw, J Michael; McFarland, Jesse M; Paavilainen, Ville O et al. (2015) Prolonged and tunable residence time using reversible covalent kinase inhibitors. Nat Chem Biol 11:525-31
Bikle, Daniel D (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319-29
Correia, Maria Almira; Wang, YongQiang; Kim, Sung-Mi et al. (2014) Hepatic cytochrome P450 ubiquitination: conformational phosphodegrons for E2/E3 recognition? IUBMB Life 66:78-88

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