OXIDATIVE STRESS RESPONSES IN PATHOGENIC PSEUDOMONAS SPECIES

致病性假单胞菌种的氧化应激反应

基本信息

批准号：
8168312
负责人：
JAMES Robert ALFANO
金额：
$ 7.08万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8168312
关键词：
Animal Model Animals Antioxidants Bacillus subtilis Bacteria Cells Complex Computer Retrieval of Information on Scientific Projects Database Escherichia coli Funding Funding Opportunities Gene Expression Genome Goals Grant Homeostasis Immune response Immune system Individual Institution Life Mediating Metabolic Molecular Organism Oxidation-Reduction Oxidative Stress Pathogenicity Plants Process Proteins Proteomics Pseudomonas Pseudomonas aeruginosa Regulation Research Research Personnel Resources Role Signal Transduction Source Stress Stress Tests System Systems Biology United States National Institutes of Health biological adaptation to stress biological systems commensal microbes pathogen trait transcriptomics

Animal Model Animals Antioxidants Bacillus subtilis Bacteria Cells Complex Computer Retrieval of Information on Scientific Projects Database Escherichia coli Funding Funding Opportunities Gene Expression Genome Goals Grant Homeostasis Immune response Immune system Individual Institution Life Mediating Metabolic Molecular Organism Oxidation-Reduction Oxidative Stress Pathogenicity Plants Process Proteins Proteomics Pseudomonas Pseudomonas aeruginosa Regulation Research Research Personnel Resources Role Signal Transduction Source Stress Stress Tests System Systems Biology United States National Institutes of Health biological adaptation to stress biological systems commensal microbes pathogen trait transcriptomics

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项目摘要

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. Stress response is the ability of an organism to adjust to drastic changes in environmental parameters. All living organisms have genetically encoded stress response and adaptation systems. Oxidative stress is a common stress form at the cellular level. Recent revolutionary progress in high-throughput experimental and computational approaches offer an opportunity to characterize the molecular mechanisms of oxidative stress response at the level of organisms, cells, genomes, regulatory networks and individual components. We propose to characterize stress response and regulation by focusing on oxidative stress response mechanisms. We will examine Pseudomonas bacterial species under conditions of oxidative stress to (i) identify and quantify gene expression changes, (ii) analyze proteomic and metabolic changes, (iii) build a global transcriptomic and proteomics networks, and (iv) characterize oxidative stress response networks. Much of the proposed research is cutting edge, has not been performed in any biological system, and it will allow for a new avenue of research for the Alfano and Becker research groups and new grant funding opportunities. Research into the mechanisms by which model organisms maintain redox homeostasis have revealed it to be an intricate and complex process. Bacterial antioxidant mechanisms are best understood in commensal Escherichia coli and the Gram-positive model organism Bacillus subtilis (saprophyte) (41), however, there are significant gaps in our understanding of redox homeostasis in non-model organisms. Here we seek to use systems biology approaches to determine if the mechanisms by which bacteria that are exposed to the intense oxidative stress response of the innate immune system vary from that of free-living or commensal bacteria. Specifically, we will use the animal pathogen Pseudomonas aeruginosa and the plant pathogen P. syringae. Both species are exposed to endogenous oxidative stress and exposed to oxidative stress from their host's innate immune response. It will be informative to compare and contrast the importance of oxidative stress responses in pathogenicity of plants and animals. A systems biology approach will allow for a greater understanding of the divergent and convergent evolutionary traits that these bacteria have acquired. We anticipate that we will identify oxidative stress response mechanisms that are common to both species. Our long-term goal is to understand how redox signals from biotic stress are mediated in Gram-negative pathogens of plants and animals to elucidate mechanisms of oxidative stress protection. The Specific Aims of this application are as follows: Identify and quantitate gene expression changes in P. aeruginosa and P. syringae under different oxidative stress conditions; Analyze proteomic and metabolic changes during oxidative stress in P. aeruginosa and P. syringae; Build global network of transcriptomic and proteomic changes induced by oxidative stress; and test role of gene products in oxidative stress response.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。压力反应是有机体适应环境参数发生急剧变化的能力。所有生物体都有遗传编码的压力反应和适应系统。氧化应激是在细胞水平上的常见应激形式。高通量实验和计算方法中最近的革命进步为表征生物，细胞，基因组，调节网络和单个组件水平上氧化应激反应的分子机制提供了一个机会。我们建议通过关注氧化应激反应机制来表征应力反应和调节。我们将在（i）识别和量化基因表达变化的条件下检查假单胞菌细菌种类，（ii）分析蛋白质组学和代谢变化，（iii）构建全球转录组和蛋白质组学网络，以及（IV）表征氧化应激响应网络。拟议的许多研究都是最前沿的，尚未在任何生物系统中进行，它将为Alfano和Becker研究小组和新的授予资金机会提供新的研究途径。研究模型生物保持氧化还原稳态的机制的研究表明，这是一个复杂而复杂的过程。最好理解细菌性抗氧化剂机制，在共生大肠杆菌和革兰氏阳性模型有机体枯草芽孢杆菌（Saprophyte）（41）中（41），但是，我们对非模型生物中氧化还原稳态的理解存在很大的差距。在这里，我们寻求使用系统生物学方法来确定暴露于先天免疫系统强烈氧化应激反应的机制是否与自由生活或共生细菌的机制不同。具体而言，我们将使用铜绿假单胞菌和植物病原体丁香假单胞菌的动物病原体。这两种物种都暴露于内源性氧化应激，并从宿主的先天免疫反应中暴露于氧化应激。比较和对比氧化应激反应在动植物的致病性中的重要性将是有益的。系统生物学方法将使对这些细菌获得的分歧和收敛性进化特征有更深入的了解。我们预计我们将确定这两种物种共有的氧化应激反应机制。我们的长期目标是了解生物胁迫的氧化还原信号如何在动植物的革兰氏阴性病原体中介导，以阐明氧化应激保护的机制。该应用的具体目的如下：在不同的氧化应激条件下，识别和定量基因表达变化；分析铜绿假单胞菌和丁香假单胞菌中氧化应激期间的蛋白质组学和代谢变化；建立由氧化应激引起的转录组和蛋白质组学变化的全球网络；基因产物在氧化应激反应中的测试作用。