PROTEOMIC CHARACTERIZATION OF ANTHRAX INFECTION IN MACACA FASCICULARIS

食蟹猴炭疽感染的蛋白质组学特征

• 批准号: 7716112
• 负责人: RAYMOND W SCHWEGLER
• 金额: $ 0.1万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716112
• 关键词: Affinity; Animal Model; Animals; Anthrax Attack; Anthrax disease; Biological; Categories; Cations; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Coupled; Disease; Disease Progression; Funding; Gel; Goals; Government; Grant; Human; Immune response; Incidence; Infection; Institution; Macaca; Macaca fascicularis; Methodology; Molecular Weight; Monitor; Outcome; Plasma; Plasma Proteins; Population; Proteins; Proteomics; Research; Research Personnel; Research Project Grants; Resources; Sampling; Source; Survivors; Testing; Time; United States National Institutes of Health; base; comparative; pathogen; tandem mass spectrometry; two-dimensional

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 炭疽是美国国立卫生研究院的A类病原体，历史上一直被政府认为是一种潜在的生物武器。 在2001年炭疽袭击之后，显然需要采取更有效的战略来监测、处理和遏制另一次袭击。 使用食蟹猴作为炭疽感染的动物模型，我们的假设是确定炭疽感染是否产生不同的，疾病相关的蛋白质（签名）容易检测血浆中的蛋白质组学方法。 该研究项目的具体目的是使用比较蛋白质组学方法来确定是否存在指示炭疽感染并提示疾病进展的差异表达食蟹猴血浆蛋白。 新发现的蛋白质可能与免疫反应或炭疽感染过程中产生的蛋白质产物直接相关，可用于预测或监测人群中的疾病进展和发病率。 为了验证我们的假设，将使用两种不同的策略。 第一种方法将包括来自感染后不同时间点的食蟹猴血浆样品的基于前期WCX（弱阳离子交换）珠的亲和捕获，然后进行MALDI-TOF/TOF分析。 通过这种方法，我们将能够确定感染后的结果（幸存者或非幸存者）和时间点是否存在特异性的不同蛋白质谱，并提供血浆样品中低分子量蛋白质的综合分析。 第二种方法将使用2D-DIGE或凝胶分析中的二维差分与串联质谱联用，以定量观察血浆样品中与疾病进展和结果相关的低质量和高质量蛋白质。我们的目标是确定蛋白质组学的变化，在血浆蛋白的食蟹猴，这将澄清机制，一些动物可以抵抗死亡后炭疽感染。