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Systems Biology approach to identify therapeutic targets in nonhuman primates exposed to Y. pestis
Author(s) -
Hoke Allison Violet,
Gautam Aarti,
Dimitrov George,
Hammamieh Rasha,
Jett Marti
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.554.9
Subject(s) - yersinia pestis , biology , nonhuman primate , host (biology) , immune system , systems biology , plague (disease) , computational biology , immunology , gene , virulence , genetics , evolutionary biology , medicine , pathology
Yesinia pestis , the etiological agent of the plague, induces vascular and pulmonary collapse in the host that is not well characterized. Y. pestis is known to have developed processes to overpower the host immune system and cause infections. In this study, a nonhuman primate model was exposed to aerosolized CO92 Y. pestis which has the potential to be used as a biological weapon. To understand the complex interaction between the pathogen and host, we have applied global ‐omics profiling to determine the basis of infections and identify host defense strategies and the mechanisms by which they are regulated. The genes, proteins, and metabolites profile show unique signatures shortly after exposure. In the infected monkeys, we identified a modified HIF‐1 pathway. We have shown profiles that have been generated from a few genes over the course of infection that are involved in molecular transport, immune response, and apoptosis. Quantitative Real‐Time PCR was utilized to validate the microarray results from blood chemistry profiles. The data from blood chemistry is also discussed. This research was supported through grant # TMTI0029_09_WR_T from the DoD Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA).