Molecular Signatures of Biological Pathogens

"The early genomic responses of human peripheral blood mononuclear cells (PBMCs) to in vitro infection with specific microbial pathogens will be assessed by DNA microarray technology. Host gene expression "signature" to microbial pathogen exposure anddistinct host responses will be characterized. Detailed in vitro studies will permit forecasting/predicting expected early molecular markers of in vivo infection with biological warfare agents of high interest with regards to bioterrorism threats (Centersfor Disease Control and Prevention [CDC] Category A biological agents). Phase I will evaluate differential immune response of PBMCs to Bacillus cereus, Bacillus subtilis, and Escherichia coli and will validate in vitro studies by evaluating in vivo immuneresponses to Bacillus anthracis vaccinations and Escherichia coli urinary tract infections. Investigation of other pathogens to generate a comprehensive database of human genomic response to various types of Gram-positive and Gram-negative bacteria andviruses will be undertaken in Phase II in a larger group of subjects at multiple sampling times after infection. Our company goals and plans are to develop a biomedical sensor (or sensors), a field kit or other device for rapid detection of earlydifferential immune responses (lymphokines, cytokines, or other serum markers) to specific microbial pathogens. Understanding the human genomic response to specific infections and identification