Transcription factor control of Entamoeba development

内阿米巴发育的转录因子控制

基本信息

批准号：
8950071
负责人：
UPINDER SINGH
金额：
$ 19.77万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8950071
关键词：
Amoeba genus Area Binding Binding Proteins Binding Sites Biological Models Biology Cause of Death Cyst DNA Data Development Disease Dominant-Negative Mutation Down-Regulation Dysentery EMSA Entamoeba Entamoeba histolytica Entamoeba invadens Etiology Exploratory/Developmental Grant Family Gene Expression Gene Expression Profile Genes Genetic Genome Genomic approach Goals Grant Health Human In Vitro Knowledge Life Cycle Stages Liver Abscess Methods Molecular Nature Organism Oxidative Stress Parasites Pathogenesis Pathway interactions Phenotype Process Protein Binding Proteins Protocols documentation Publications RNA Interference Role Signal Transduction Staging System Tissues Transcriptional Regulation Transfection Virulence Work base biological adaptation to stress disease transmission enteric pathogen excystation experience genetic approach genetic manipulation high risk insight metabolomics method development new therapeutic target novel pathogen prevent promoter public health relevance success tool development transcription factor transmission process

项目摘要

DESCRIPTION (provided by applicant): Entamoeba histolytica, a protozoan parasite, is an important human pathogen. Diseases caused by E. histolytica include dysentery and liver abscesses, and this organism is a leading parasitic cause of death on a global scale. The life cycle of Entamoeba involves stage inter-conversion between trophozoites and cysts. Importantly, the conversion to cysts allows the pathogen to disseminate to new hosts while development to trophozoites allows the organism to cause invasive disease in the host. Thus, stage interconversion is essential for disease transmission and pathogenesis. However, despite being central to amebic biology, stage conversion is poorly understood. Many factors have contributed to the paucity of data including the inability to reproduce the developmental cycle in E. histolytica. Instead, the reptilian ameba E. invadens, which has the same disease pathogenesis as E. histolytica, has been used as a model system to study Entamoeba development. In E. invadens, both encystation and excystation can be recapitulated with high efficiency in vitro. However, until recently a poorly annotated genome and lack of methods for genetic manipulation have prevented full exploitation of this system. The recent re-sequencing of the E. invadens genome, publication of the transcriptome of stage conversion, and development of methods for constitutive and regulated gene expression open up new avenues for discovery. We aim to build upon these recent successes by studying transcription factors that regulate stage conversion as a means to identify pathways that regulate encystation. We will (i) characterize two known transcription factors to determine their roles in controlling stage conversion, and (ii) identify a new transcription factor that controls genes regulated during early encystation. These data will allow us to gain the first insights into the molecular mechanisms that regulate Entamoeba development and could give important insights into methods for blocking this transition or new targets for therapeutics. Dissecting the developmental cascade is crucial to understanding the biology of this important human pathogen.

描述（由适用提供）：原生动物寄生虫Entamoeba Histolictica是一种重要的人类病原体。由E. astolytica引起的疾病包括痢疾和肝脓肿，这种生物是全球范围内的主要寄生虫死亡原因。 Entamoeba的生命周期涉及滋养体和囊肿之间的阶段相互转化。重要的是，向囊肿的转化使病原体可以传播到新宿主，而发展为滋养体可以使生物体在宿主中引起侵入性疾病。这是阶段互连对于疾病传播和发病机理至关重要的。然而，尽管对阿米比克生物学是核心，但阶段转换知之甚少。许多因素导致数据缺乏，包括无法再现组织溶液性的发育周期。取而代之的是，具有与Histolytica E. histolictica相同的疾病发病机理的复制品Ameba E. Invadens已被用作研究肠发展的模型系统。在E. Inscadens中，可以通过体外高效率概括百科全书和外观。然而，直到最近，注释不足的基因组和缺乏基因操纵方法还阻止了该系统的完全开发。 E.的最新重新测试使基因组，阶段转化的转录组的发表以及构成性和受调节基因表达的方法的发展开辟了新的发现途径。我们旨在通过研究调节阶段转换为识别调节百货公司的途径的转录因子来基于这些最近的成功。我们将（i）表征两个已知的转录因子，以确定它们在控制阶段的作用转化率和（ii）确定一个控制早期调节基因的新转录因子 encystation。这些数据将使我们能够对调节Entamoeba发育的分子机制获得首次见解，并可以为阻止这种过渡或新靶标的方法提供重要的见解。解剖发育级联对于理解这种重要人类病原体的生物学至关重要。