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A Systems Biology Approach to Infectious Diseases Research


EMSL Project ID
37504

Abstract

We describe an integrated program for coupling advanced capabilities in high-throughput transcriptomics, proteomics, and metabolomics with a comprehensive informatics infrastructure and a sophisticated approach to computational reconstruction and modeling of metabolic and gene regulatory networks. These powerful tools will be directed at delineating the mechanisms by which two related pathogens, Salmonella and Yersinia, adapt to the intracellular environment upon infecting macrophages and then manipulate that environment to facilitate their own survival and replication. The insights derived from modeling these behaviors may lead to the identification of novel therapeutic targets. The overall objectives are to: 1) Develop genome-scale metabolic and regulatory network reconstructions for Salmonella and Yersinia to provide the computational foundation for our systems biology approach; 2) Develop and disseminate 'sample matched' global datasets for Salmonella and Yersinia using transcriptomics, proteomics, and metabolomics technologies to provide the experimental foundation for our systems biology approach; 3) Produce and characterize knock-out mutations in regulatory genes predicted to be essential for systemic infection in mouse models for Salmonella enterica and Yersinia pestis; and 4) Use the network reconstructions, omics results, and phenotype changes in knock-out mutants to refine computational models of pathogenesis for Salmonella and Yersinia.

EMSL world class capabilities in proteomics, NMR for structure and metabolomics, and advanced computation are well recognized. While all of these areas are included in the proposal the real benefit of using EMSL's capabilities is the team oriented nature of the operations; the project described above requires multiple-disciplines and multiple-strategies. These capabilities with the high quality team are why we request to perform this research in collaboration with EMSL.

Project Details

Project type
Exploratory Research
Start Date
2009-09-14
End Date
2010-09-19
Status
Closed

Team

Principal Investigator

Joshua Adkins
Institution
Pacific Northwest National Laboratory

Team Members

Ernesto Nakayasu
Institution
Pacific Northwest National Laboratory

Charles Ansong
Institution
National Institutes of Health

Vladimir Motin
Institution
University of Texas Medical Branch

Bernhard Palsson
Institution
University of California, San Diego

Thomas Metz
Institution
Pacific Northwest National Laboratory

Fred Heffron
Institution
Oregon Health & Science University

Robert Heck
Institution
Pacific Northwest National Laboratory

Kathleen McAteer
Institution
Washington State University Tri-Cities

Garry Buchko
Institution
Pacific Northwest National Laboratory

John Cort
Institution
Pacific Northwest National Laboratory

Related Publications

Qiu Y, BK Cho, YS Park, DR Lovley, BO Palsson, and K Zengler. 2010. "Structural and Operational Complexity of the Geobacter Sulfurreducens Genome." Genome Research 20:1304-1311. doi:10.1101/gr.107540.110