Discovery of Novel Virulence Factors of Biothreat Agents: Validation of the Phosphoproteome-Based Approach
Annual rept. 1 Jun 2006-31 May
GEORGE MASON UNIV FAIRFAX VA
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We are developing a novel application of Reverse Phase Protein Microarrays RPMA technology to the study of biothreat organisms. The power of this technology to survey the phosphorylation status of multiple proteins simultaneously enables us to map the host cell response to infection with multiple strains and species of Francisella as well as to begin to dissect which individual factors or proteins are contributing to the complex signals generated during infection, and thereby perhaps also to virulence. We will demonstrate the utility of this technology to examine host responses to bacterial infection, host responses to extracellular macromolecules, and host responses to individual proteins applied either extracellularly or intracellularly to the host cell. We will also compare different strains and species of Francisella using RPMA to elucidate the molecular differences in host response to the strains. Furthermore, we will begin to establish a model of how to use RPMAs to screen a genome-worth of open reading frames ORFs for potential virulence factors VFs by identifying those factors with an effect on host cell signaling pathways.
- Medicine and Medical Research
- Chemical, Biological and Radiological Warfare