SBIR-STTR Award

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 and distinct 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 (Centers for 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 immune responses 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 and viruses 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 early differential immune responses (lymphokines, cytokines, or other serum markers) to specific microbial pathogens. Understanding the human genomic response to specific infections and identification of key molecular markers will allow rapid detection of human exposure to specific microbial pathogens and biological warefare agents to allow early intervention. These findings will enable development of biosensors to rapidly detect early human exposure to biological agents which will have tremendous utility both within the DOD and the private sector (both nationally and internationally).

The early genomic responses of human peripheral blood mononuclear cells (PBMCs) to in vitro infection with specific microbial pathogens are being assessed by DNA microarray technology to determine host gene expression "signatures" to pathogen exposure and distinct host responses. Detailed in vitro studies will permit forecasting of molecular markers of in vivo infection with biological warfare agents of high interest with regards to bioterrorism threats. Phase I is evaluating differential immune response of PBMCs to Bacillus cereus, Bacillus subtilis, and Escherichia coli and validating them against in vivo immune responses to Bacillus anthracis vaccinations and Escherichia coli urinary tract infections. Investigation of other pathogens to generate a more comprehensive database of human response to Gram-positive and Gram-negative bacteria and viruses will be undertaken in Phase II. The genomic database of human response to various pathogens will be used to identify proteomic patterns that distinguish specific infections. Since proteins direct all biological functions and change during infection processes, determining these marker proteins directly in blood samples could rapidly diagnose specific infections. We are working to develop biosensors for rapid detection of early differential immune responses to specific pathogens. Our findings will have tremendous utility within the DOD and the private sector. Rapid and accurate identification of human exposure to infectious pathogens and biological warfare agents. Development of a biomedical sensor, a field kit or other device for rapid detection of early differential immune response to specific microbial pathogens

Keywords:
microbial pathogens, immune response, proteomics, genomics, bioterrorism, biosensors, dna microarray, molecular markers