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
Released Data Link
Team
Principal Investigator
Team Members
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