Systems analysis of oxygen regulation in Halobacterium

盐杆菌氧调节的系统分析

• 批准号: 7158160
• 负责人: Amy K Schmid
• 金额: $ 4.6万
• 依托单位: INSTITUTE FOR SYSTEMS BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-16 至 2008-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158160
• 关键词: DNA damage; Halobacteriaceae; bacterial genetics; binding sites; bioinformatics; chromatin immunoprecipitation; crosslink; environmental adaptation; environmental stressor; gel mobility shift assay; gene deletion mutation; genetic regulation; genetic transcription; high throughput technology; homeostasis; microarray technology; oxidative stress; oxygen; phenotype; postdoctoral investigator; proteomics; statistics /biometry; technology /technique development; transcription factor

DESCRIPTION (provided by applicant): To withstand environmental onslaught, biological systems mount global programs to coordinate the induction of protection and repair mechanisms. This proposal poses the hypothesis that the transcriptional networks underlying such responses to diverse stressors are interrelated. Halobacterium, a halophilic archaeon, has been chosen as a model for this study because it routinely negotiates an array of adverse conditions in its extreme environment, including anoxia, metal stress, and radiation damage. This proposal will investigate the inter-relationship of these responses using global approaches. Given that basal genetic information processing pathways in Halobacterium are mediated by eukaryotic-like proteins, findings from this study will have a direct impact on understanding how complex eukaryotic organisms elicit orthogonal responses in disease-perturbed or infection states. Specifically, I will (1) Characterize key transcriptional regulators responsible for mediating responses to fluctuating oxygen concentrations and identify regulons under their direct and indirect control; (2) Through statistical analysis of integrated datasets, evaluate the extent of cross-regulation of the anoxic response with other environmental perturbations; (3) Experimentally test new hypotheses generated by statistical analysis. These proposed experiments are expected to result in a transcriptional network model that addresses how organisms maintain homeostasis despite stress.

描述（由申请人提供）：为了承受环境冲击，生物系统启动了全球计划，以协调保护和维修机制的诱导。该提议提出了这样的假设，即这种对不同压力源的反应背后的转录网络相互关联。盐酸盐是一种卤素考古，已被选为本研究的模型，因为它在极端环境中通常会协商一系列不利条件，包括缺氧，金属应力和辐射损伤。该建议将使用全球方法研究这些响应的相互关系。鉴于大杆菌中的基础遗传信息处理途径是由真核样蛋白介导的，因此这项研究的发现将直接影响理解复杂的真核生物如何引起疾病扰动或感染状态中的正交反应。具体而言，我将（1）表征负责介导对氧气浓度波动的反应的关键转录调节器，并在其直接和间接控制下识别调节； （2）通过综合数据集的统计分析，评估缺氧反应与其他环境扰动的交叉调节程度； （3）通过统计分析产生的实验测试新假设。这些提出的实验预计将导致转录网络模型，该模型解决了尽管压力压力，但仍能解决生物如何保持体内平衡。