Knowledge of bacterial gene function is crucial to making progress in biomedical research that relies on genomic information. Experimental discovery and validafion of gene function is the foundation on which all gene funcfional annotation is based. Gene annotafion is propagated forward by bioinformatics methods from these experimentally validated genes to all sequenced genomes. In reverse, bioinformafics methods are used to collate informafion about genes, including sequence domains, motifs, etc. in order to infer possible functions that require validation. The Data Management Core will assist the projects in both directions by development and use of web-based database and bioinformatics software applications. A laboratory information management system (LIMS) will be constructed that records and displays informafion about candidate gene experiments in order to coordinate project acfivifies and share information among investigators. Web-based database applications will be developed to integrate and display experimental results with annotation of Acinetobacter baumannii genomes and bioinformatics predictions, along with search functionality to support database queries. Bioinformatics applications will also be applied or created that will improve the quality of gene identification in Ab sequences, update Ab genome annotation, determine the prevalence of target genes across bacterial species, collate bioinformatics predicfions and database searches to increase knowledge about target proteins and idenfify gene functional units (conserved gene clusters). These tools will assist project Pis with interpretation of experimental results, the identification of new target genes and sRNAs for experimental research, and sharing of results with the broader research community.

Public Health Relevance

Information resources will be developed by the Data Management core that will enable the interpretation of experimental results in the broader context of bacterial genomics to uncover potential sources of antibiotic susceptibility in Acinetobacter baumannii, the determination of the prevalence of assayed Ab genes in other pathogenic bacteria in order to prioritize research targets according to their range of occurrence, and the dissemination of research results to the broader research community.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI107775-01
Application #
8597724
Study Section
Special Emphasis Panel (ZAI1-FDS-M (M1))
Project Start
Project End
Budget Start
2013-06-24
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$108,131
Indirect Cost
$39,087
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Karalewitz, Andrew P-A; Miller, Samuel I (2018) Multidrug-Resistant Acinetobacter baumannii Chloramphenicol Resistance Requires an Inner Membrane Permease. Antimicrob Agents Chemother 62:
Chavez, Juan D; Lee, Chi Fung; Caudal, Arianne et al. (2018) Chemical Crosslinking Mass Spectrometry Analysis of Protein Conformations and Supercomplexes in Heart Tissue. Cell Syst 6:136-141.e5
Vreven, Thom; Schweppe, Devin K; Chavez, Juan D et al. (2018) Integrating Cross-Linking Experiments with Ab Initio Protein-Protein Docking. J Mol Biol 430:1814-1828
Zhong, Xuefei; Navare, Arti T; Chavez, Juan D et al. (2017) Large-Scale and Targeted Quantitative Cross-Linking MS Using Isotope-Labeled Protein Interaction Reporter (PIR) Cross-Linkers. J Proteome Res 16:720-727
Gallagher, Larry A; Lee, Samuel A; Manoil, Colin (2017) Importance of Core Genome Functions for an Extreme Antibiotic Resistance Trait. MBio 8:
Schweppe, Devin K; Chavez, Juan D; Lee, Chi Fung et al. (2017) Mitochondrial protein interactome elucidated by chemical cross-linking mass spectrometry. Proc Natl Acad Sci U S A 114:1732-1737
Wu, Xia; Chavez, Juan D; Schweppe, Devin K et al. (2016) In vivo protein interaction network analysis reveals porin-localized antibiotic inactivation in Acinetobacter baumannii strain AB5075. Nat Commun 7:13414
Miller, Samuel I (2016) Antibiotic Resistance and Regulation of the Gram-Negative Bacterial Outer Membrane Barrier by Host Innate Immune Molecules. MBio 7:
Baric, Ralph S; Crosson, Sean; Damania, Blossom et al. (2016) Next-Generation High-Throughput Functional Annotation of Microbial Genomes. MBio 7:
Chavez, Juan D; Schweppe, Devin K; Eng, Jimmy K et al. (2016) In Vivo Conformational Dynamics of Hsp90 and Its Interactors. Cell Chem Biol 23:716-26

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