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Tools for regulated gene expression in Entamoeba invadens

内阿米巴入侵基因表达调控工具

基本信息

批准号：
8998927
负责人：
UPINDER SINGH
金额：
$ 20.06万
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：
2015-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8998927
关键词：
Amoeba genus Biological Models Biological Process Biology Cause of Death Cells Communities Cyst Data Development Developmental Biology Disease Dissection Dominant-Negative Mutation Dysentery Entamoeba Entamoeba histolytica Entamoeba invadens Etiology Exploratory/Developmental Grant Funding Gene Expression Gene Proteins Gene Silencing Generations Genetic Genetic study Genome Genomics Goals Grant Health Human In Vitro Knowledge Life Cycle Stages Liver Abscess Messenger RNA Methods Molecular Organism Parasites Pathogenesis Pathway interactions Phenotype Ploidies Process Proteins Protocols documentation Publications Publishing RNA Interference Reagent Regulation Role Small RNA Staging Syndrome System Technology Transfer Tetanus Helper Peptide Tissues Transfection Work base disease transmission enteric pathogen excystation experience gene replacement genetic manipulation interest metabolomics method development pathogen prevent promoter protein expression routine practice success tool transcriptome transmission process vector

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 gene expression open up new avenues for discovery. We aim to build upon these recent successes by establishing new tools for the study of E. invadens including (i) regulated gene expression, (ii) gene silencing, and (iii) development of negative selection and single cell markers. These methods will make possible new experimental strategies for studying Entamoeba stage conversion, and greatly aid the entire Entamoeba community. Dissecting the developmental cascade is crucial to understanding the biology of this important human pathogen.

描述（由申请方提供）：溶组织内阿米巴是一种原生动物寄生虫，是一种重要的人类病原体。E.溶组织菌包括痢疾和肝脓肿，这种生物体是全球范围内主要寄生虫致死原因。内阿米巴的生活史包括滋养体和包囊之间的阶段相互转换。重要的是，转化为包囊允许病原体传播到新的宿主，而发育为滋养体允许生物体在宿主中引起侵入性疾病。因此，阶段转换对于疾病传播和发病是必不可少的。然而，尽管是核心阿米巴生物学，阶段转换是知之甚少。许多因素导致了数据的缺乏，包括不能再现E。溶组织剂相反，爬行动物阿米巴E. invadens的致病机理与E. histolytica已被用作研究内阿米巴发育的模型系统。在大肠在体外，无论是包囊还是脱囊，都可以高效地再现入侵体。然而，直到最近，一个注释不佳的基因组和缺乏遗传操作的方法，阻止了充分利用这一系统。最近对E. invadens基因组，阶段转换的转录组的出版，以及组成型基因表达方法的发展开辟了新的发现途径。我们的目标是建立在这些最近的成功，建立新的工具，为研究E。入侵的研究包括（i）调节基因表达，（ii）基因沉默，和（iii）负选择和单细胞标记物的开发。这些方法将为研究内阿米巴阶段转换提供新的实验策略，并极大地帮助整个内阿米巴群落。剖析发育级联对于理解这种重要的人类病原体的生物学至关重要。