Discovery of Novel Virulence Factors of Biothreat Agents: Validation of the Phosphoproteome-Based Approach

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2007
Accession Number
ADA470906

Entities

People

  • Charles L. Bailey
  • Monique van Hoek

Organizations

  • George Mason University

Tags

DTIC Thesaurus Topics

  • Adaptive Immunity
  • Apoptosis
  • Bacteria
  • Bacterial Infections
  • Biological Toxins
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Data Analysis
  • Immune System
  • Microbiology
  • Pathogenic Bacteria
  • Peptide Growth Factors
  • Protein Microarrays
  • Proteins
  • Proteomics
  • Therapy

Fields of Study

  • Biology

Readers

  • Infectious Disease/Epidemiology
  • Molecular Genetics