Developing Tools to Study Encystation in Entamoeba Histolytica

描述（由申请方提供）：原生动物寄生虫溶组织内阿米巴每年造成约5000万例侵袭性疾病，是全球第二大寄生虫性死因。阿米巴感染最常见的表现是结肠疾病（痢疾）和肝脓肿。除了生命的丧失，还有与阿米巴痢疾相关的显著发病率！疾病，特别是儿童往往患有营养不良和发育迟缓。E.溶组织剂被归类为生物恐怖主义关注的B类制剂，恶意使用可能导致显著的发病率。寄生虫的生命周期包括从滋养体到包囊阶段的转变。这种转化对于疾病传播至关重要，但目前人们对这种转化的了解极少。我们的目标是开发研究E.溶组织发育生物学第一个目标是建立大肠杆菌全基因组转录谱。溶组织囊肿和滋养体。将使用体内包囊和相关的脱囊滋养体进行包囊转录谱分析，并将提供包囊和滋养体特异性基因的首次全基因组鉴定。第二个目的是建立一种体外包囊化的方法。溶组织剂我们将利用E.溶组织菌（histolytica），其可能倾向于成囊，使它们在模拟结肠环境的条件下生长，并将它们暴露于在相关系统中引起成囊的刺激。成功开发体外成囊将使我们能够剖析这种寄生虫发育生物学的关键方面，包括识别触发成囊的途径。这些方法有望为E. histolytica，并将铺平道路，进一步表征的发展计划，在这种寄生虫。与公共卫生的相关性：溶组织内阿米巴是一种重要的病原体，在全球范围内对人类健康产生影响。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的生命阶段，目的是确定诊断，治疗和预防人类感染的新方法。

DESCRIPTION (provided by applicant): The protozoan parasite Entamoeba histolytica causes an estimated 50 million cases of invasive disease annually and is the second leading parasitic cause of death worldwide. The most common manifestations of amebic infection are colonic disease (dysentery) and liver abscesses. In addition to the lives lost there is significant morbidity associated with amebic diarrhea! illness, especially in children who often suffer from malnourishment and growth retardation. E. histolytica is classified as a Class B agent of concern for bioterrorism and malicious use could result in significant morbidity. The parasite's life cycle involves conversion from the trophozoite to the cyst stage. This conversion, which is essential for disease propagation, is extremely poorly understood at present. Our goals are to develop tools to study E. histolytica developmental biology. The first aim is to develop a genome-wide transcriptional profile of E. histolytica cyst and trophozoites. The cyst transcriptional profiling will be performed using in vivo cysts and the associated excysted trophozoites and will provide the first genome- wide identification of cyst and trophozoite-specific genes. The second aim is to develop a method for in vitro encystation in E. histolytica. We will utilize strains of E. histolytica, which may be predisposed to encyst, grow them in conditions that mimic the colonic environment, and expose them to stimuli that cause encystation in related systems. Successful development of in vitro encystation will allow us to dissect key aspects of the developmental biology of this parasite including identification of the pathways that trigger encystation. These approaches promise to provide the first insights into differentiation in E. histolytica and will pave the way for further characterization of the development program in this parasite. Relevance to public health: Entamoeba histolytica is an important pathogen and has an impact on human health on a global scale. 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 life stages of the parasite with the goal of identifying new ways to diagnose, treat, and prevent human infections.