Identification of Changes in Gene Expression Induced by Toxic Agents: Implications for Therapy and Rapid Diagnosis.

摘要

In our changing world, there has been a significant increase in both the nature and degree of the threat posed by the use of biological agents. Studies for many years have focused on rapid detection of known biological threat agents using structural-based probes designed and directed toward features of the pathogenic agent. However, concerns relating to unidentifiable pathogens, that could result from either deliberate or natural mutation processes have prompted studies to find alternative approaches. Our thesis was that an exposed individual would show gene expression responses unique to the pathogenic agent and prior to onset of the full illness. Therefore this study focused on use of peripheral blood mononuclear cells (PBMC) as a readily accessible reservoir of historical information for development of a library of host gene expression responses to known biological threat agents. The gene responses seen in this accessible tissue would be a compilation of both primary and secondary effects on PBMC and would present a signature pattern of a specific biological threat agent. This study describes our work to establish a library of host responses to pathogenic agents for use to (a) predict the course of impending illness especially for unidentifiable pathogens so that appropriate therapeutic intervention can be initiated, (b) to characterize the degree of individual exposure in order to assist health personnel to rapidly differentiate those who will become seriously ill from the worried well individuals and (c) reveal new therapeutic targets that can be initiated even in late- stage illness caused by biological threat agents.