The goal of this proposal is to secure funds to purchase a multi-tiered proteomic compute (MFC) cluster for University of Washington Health Sciences Center-based principal investigators engaged in biomedical research. The MPC will be located in the School of Pharmacy Mass Spectrometry (SOP MS) facility in the Health Sciences Center, which serves as a fee-for-service operation for UW Pi's wishing to conduct proteomic experiments, and is the only such facility on the UW campus. The SOP MS facility currently has a 10-node compute cluster for processing mass spectrometry-based proteomic experiments, but none for protein folding. The MPC will expand this capability 20-fold. Both traditional hypothesis-driven protein chemistry research and hypothesis-generating research enabled by proteomic techniques will utilize the MPC cluster. All aspects of proteomic and protein chemistry-based research will be supported. For example, we will use it to: 1) fold individual proteins de novo, 2) fold entire proteomes de novo, 3) elucidate protein-protein interactions via chemical cross-linking, 4) map out sub- cellular protein locations, 5) search for multiple anticipated post-translation modifications (PTM's) on individual proteins, 6) search MS-based proteomic data for multiple unsuspected PTM's, and 7) define proteomes. Initially, the MPC cluster will be for support of researchers in the Schools of Pharmacy, Medicine, and Public Health; eventually, however, any PI on campus or from the Seattle region utilizing the SOP MS facility will be given access to the compute power. Initial projects include the following areas of biomedical research: 1) acute respiratory distress syndrome (ARDS) and other lung injury diseases under investigation at the UW- affiliated Harbor view Medical Center, 2) prions and prion folding, 3) Apolipoprotein PTM's, 4) protein-protein cross-linking, 5) vaccine candidates and therapeutic targets in Gram-negative organisms, 6) sub cellular mapping of proteins under conditions of drug-induced liver disease, and 8) toxic-proteomics. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR023044-01
Application #
7125813
Study Section
Special Emphasis Panel (ZRG1-BST-D (30))
Program Officer
Tingle, Marjorie
Project Start
2006-08-01
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2008-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$500,000
Indirect Cost
Name
University of Washington
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Cheng, Chin Jung; Daggett, Valerie (2014) Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH. Biomolecules 4:181-201
Jung, Sunhee; Smith, Jennifer J; von Haller, Priska D et al. (2013) Global analysis of condition-specific subcellular protein distribution and abundance. Mol Cell Proteomics 12:1421-35
Mattes, Timothy E; Nunn, Brook L; Marshall, Katharine T et al. (2013) Sulfur oxidizers dominate carbon fixation at a biogeochemical hot spot in the dark ocean. ISME J 7:2349-60
Karadzic, Ivanka; Maupin-Furlow, Julie; Humbard, Matthew et al. (2012) Chemical cross-linking, mass spectrometry, and in silico modeling of proteasomal 20S core particles of the haloarchaeon Haloferax volcanii. Proteomics 12:1806-14
Hengel, Shawna M; Goodlett, David R (2012) A Review of Tandem Mass Spectrometry Characterization of Adenosine Diphosphate-Ribosylated Peptides. Int J Mass Spectrom 312:114-121
McCully, Michelle E; Beck, David A C; Daggett, Valerie (2012) Multimolecule test-tube simulations of protein unfolding and aggregation. Proc Natl Acad Sci U S A 109:17851-6
Moore, Eli K; Nunn, Brook L; Goodlett, David R et al. (2012) Identifying and tracking proteins through the marine water column: insights into the inputs and preservation mechanisms of protein in sediments. Geochim Cosmochim Acta 83:324-359
Merkley, Eric D; Daggett, Valerie; Parson, William W (2012) A temperature-dependent conformational change of NADH oxidase from Thermus thermophilus HB8. Proteins 80:546-55
Roberts, Arthur G; Yang, Jing; Halpert, James R et al. (2011) The structural basis for homotropic and heterotropic cooperativity of midazolam metabolism by human cytochrome P450 3A4. Biochemistry 50:10804-18
Chu, Lichieh Julie; Yang, Hanyin; Shih, Peiyin et al. (2011) Metabolic capabilities and systems fluctuations in Haloarcula marismortui revealed by integrative genomics and proteomics analyses. J Proteome Res 10:3261-73

Showing the most recent 10 out of 25 publications