PROTEOMIC CHARACTERIZATION OF ANTHRAX INFECTION IN MACACA FASCICULARIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anthrax is a NIH category A pathogen which has historically been considered by the government to be a potential biological weapon. Following the anthrax attacks of 2001 it is clear that more effective strategies to monitor, treat and contain another attack are necessary. Using cynomolgus macaques as an animal model for anthrax infection our hypothesis is to determine whether anthrax infection produces distinct, disease-associated proteins (signatures) readily detectable in plasma by proteomic methodologies. The specific aim of the research project is to use a comparative proteomic approach to determine whether there are differentially expressed cynomolgus macaque plasma proteins indicative of anthrax infection and suggestive of disease progression. Newly identified proteins may be directly related to immune response, or protein products produced during the course of anthrax infection and applicable for predicting or monitoring disease progression and incidence in human populations. To test our hypothesis two different strategies will be utilized. The first approach will include an upfront WCX (weak cation exchange) bead based affinity capture of the cyno plasma samples from various time points post-infection followed by MALDI-TOF/TOF analysis. With this approach we will be able to determine whether there are distinct protein profiles specific to outcome (survivor or non-survivor) and time point following infection as well as provide a comprehensive analysis of the lower molecular weight proteins within the plasma samples. The second approach will use a 2D-DIGE or two dimensional differential in gel analysis coupled with tandem mass spectrometry to gain a quantitative look at both the low and high mass proteins within plasma samples in relation to disease progression and outcome. Our goal is to identify changes proteomically in the plasma proteins of the cynos which will clarify the mechanism by which some animals can resist death following anthrax infection.