Integromic Approaches to define Networks and Biomarkers to Pathogens

Abstract

To understand the complex interaction between various biological pathogens and the host, we have applied global gene profiling to determine basis of infectious or bio-threat induced diseases and to identify host defense strategies and the mechanisms by which they are regulated. Yersinia pestis, the causative agent of plague, is known to develop strategies to overcome the host immune mechanisms and survive in the host. The objectives of our study is to identify the progression of regulatory networks and correlate with the potential stage-appropriate therapeutic targets. We exposed non-human primates by aerosol to CO92 Y. pestis/sham and determine systemic progression of illness, characterizing the dynamics of regulatory networks that will enable outlining the biochemical basis that eventually leads to lethality from Y. pestis. We have collected whole blood, plasma and various tissues from infected and control NHPs. We have characterized gene expression profiles after the infection of Y. pestis in NHPs. We are also analyzing the host metabolomic, proteomic and miRNA profiles. Our preliminary results identified early and late biomarkers of exposure to Y.pestis in the blood, lungs, spleen and lymph nodes of exposed animals. We have identified HIF-1 pathway to be altered in the infected monkeys. We have also characterized channels and transport mechanisms are involved in the pathogenesis.