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Identification of Transcriptional Regulatory Networks in Entamoeba Histolytica

溶组织内阿米巴转录调控网络的鉴定

基本信息

批准号：
7479765
负责人：
UPINDER SINGH
金额：
$ 19.37万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-15 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7479765
关键词：
3&apos Untranslated Regions Affect Amebic Liver Abscess Amebic colitis Amoeba genus Animal Model Applications Grants Binding Proteins Bioinformatics Biological Assay Biology Bispecific Antibody 2B1 Cessation of life Colitis Colon Complex Condition Cyst Cysteine Protease Developed Countries Developing Countries Development Disease Dysentery Electrophoretic Mobility Shift Assay Entamoeba histolytica Event Gene Expression Gene Family Genes Genetic Genomics Genus Cola Goals Grant Health Heat-Shock Response Hepatic Human Infection Invasive Knowledge Life Liver Abscess Luciferases Molecular Nuclear Extract Numbers Parasites Pathogenesis Principal Investigator Process Published Comment Regulation Regulatory Pathway Reporter Genes Research Infrastructure Staging System Techniques Thinking Tissues Transcriptional Regulation Tsunami Virulence Virulence Factors Virulent Water Purification Work base biological adaptation to stress concept follow-up genome sequencing in vivo insight interest mouse model new technology novel pathogen programs promoter social success

项目摘要

DESCRIPTION (provided by applicant): Transcriptional control allows coordinated expression of genes involved in similar processes or life stages. Entamoeba histolytica is a leading cause of parasitic death, but little is known about the virulence program that this protozoan parasite uses to cause invasive colonic or hepatic disease. Although a great deal of information is available on transcriptional regulatory mechanisms in model organisms, there is limited knowledge about such mechanisms in most parasite systems. The long-term goals of our lab are to understand how parasite genetics and gene expression affect virulence. Our goal is to identify transcriptional regulatory networks that control expression of virulence associated gene subsets in E. histolytica. The identification of transcriptional regulatory mechanisms in E. histolytica will give an insight into the basic biology of this parasite, as well as provide avenues for studying the regulation of amebic genes. In Aim 1 we will identify promoter motifs that allow coordinated expression of genes involved in virulence. Additionally, we will look for conserved motifs in the 3'UTR and downstream genomic regions of the gene sets of interest. Our definition of "virulence" includes the cysteine proteinase genes (involved in tissue invasion), genes involved in the stress response in ameba (Ehssp gene family), genes differentially expressed in virulent and non-virulent E. histolytica strains, genes regulated in vivo in an animal model of colitis, and genes regulated during parasite development. In Aim 2, we will functionally characterize potential regulatory motifs from the cysteine proteinase, Ehssp, and the strain-specific gene families using reporter gene and electrophoretic mobility shift assays. Success in these aims will allow us to show proof of concept that our approach is valid. Motifs that control expression of genes regulated during an animal model of colitis and during development will be characterized at a later date as those are technically much more challenging and will require the development of novel technologies in E. histolytica. This work will identify global transcriptional regulatory networks that control expression of amebic genes associated with virulence and provide a framework for characterization of the transcriptional machinery in Entamoeba histolytica. Entamoeba histolytica is an important pathogen and has an impact on human health on a global scale. The main disease manifestations are dysentery and liver abscesses. Although the majority of disease is in developing countries, this parasite can cause infections anywhere that water purification systems get adversely affected. Events such as the Tsunami or upheaval in the political and social infrastructure of a region can allow disease to emerge. We are interested in understanding the molecular mechanisms that the parasite uses to cause disease.

描述（由申请人提供）：转录控制允许参与相似过程或生命阶段的基因的协调表达。溶组织内阿米巴是导致寄生虫死亡的主要原因，但对这种原生动物寄生虫用于引起侵袭性结肠或肝脏疾病的毒力程序知之甚少。虽然大量的信息是可利用的模式生物的转录调控机制，在大多数寄生虫系统中的这种机制的知识有限。我们实验室的长期目标是了解寄生虫遗传学和基因表达如何影响毒力。我们的目标是确定转录调控网络，控制表达的毒力相关基因亚型在大肠杆菌。溶组织剂对E. histolytica将使我们深入了解这种寄生虫的基本生物学，并为研究阿米巴基因的调节提供途径。在目标1中，我们将确定启动子基序，允许参与毒力的基因的协调表达。此外，我们将寻找目标基因组的3'UTR和下游基因组区域中的保守基序。毒力的定义包括半胱氨酸蛋白酶基因（参与组织侵袭）、阿米巴应激反应基因（Ehssp基因家族）、毒力和非毒力阿米巴中差异表达的基因。溶组织菌株中的基因、结肠炎动物模型中体内调节的基因和寄生虫发育过程中调节的基因。在目标2中，我们将功能性地表征潜在的半胱氨酸蛋白酶，Ehssp，和应变特异性基因家族的报告基因和电泳迁移率变动分析的调控基序。这些目标的成功将使我们能够证明我们的方法是有效的。在结肠炎动物模型和发育过程中控制基因表达的基序将在以后的日期进行表征，因为这些基序在技术上更具挑战性，需要在大肠杆菌中开发新技术。溶组织剂这项工作将确定全球的转录调控网络，控制与毒力相关的阿米巴基因的表达，并提供了一个框架，在溶组织内阿米巴的转录机制的表征。溶组织内阿米巴是一种重要的病原体，在全球范围内影响人类健康。主要临床表现为痢疾、肝火旺。虽然大多数疾病发生在发展中国家，但这种寄生虫可以在任何地方引起感染，从而对水净化系统产生不利影响。海啸或一个地区的政治和社会基础设施动荡等事件可能导致疾病的出现。我们有兴趣了解寄生虫用于引起疾病的分子机制。