Developing Tools to Study Encystation in E Histolytica

描述(申请人提供)：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死亡原因。阿米巴感染最常见的表现是结肠病(痢疾)和肝脓肿。除了失去的生命之外，阿米巴腹泻还有很大的发病率！疾病，特别是经常营养不良和发育迟缓的儿童。溶解组织杆菌被归类为生物恐怖主义关注的B类制剂，恶意使用可能导致严重的发病率。寄生虫的生命周期包括从滋养体到包囊阶段的转换。这种转化对疾病传播至关重要，目前人们对此知之甚少。我们的目标是开发研究溶组织棘球藻发育生物学的工具。第一个目标是建立溶组织棘球菌囊和滋养体的全基因组转录图谱。包囊转录图谱将使用活体包囊和相关的外生滋养体进行，并将首次在全基因组范围内鉴定包囊和滋养体特异基因。第二个目的是建立一种体外包囊化溶组织乳杆菌的方法。我们将利用可能容易包囊的溶组织埃希氏菌菌株，在模拟结肠环境的条件下培养它们，并将它们暴露在相关系统中导致包囊的刺激下。体外囊化的成功开发将使我们能够剖析这种寄生虫发育生物学的关键方面，包括识别触发囊化的途径。这些方法有望为溶组织埃希氏菌的分化提供第一个洞察力，并将为进一步描述这种寄生虫的发育计划铺平道路。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有影响。尽管大多数疾病发生在发展中国家，但这种寄生虫可以在水净化系统受到不利影响的任何地方引起感染。诸如海啸或一个区域的政治和社会基础设施的剧变等事件可能会导致疾病的出现。我们对了解寄生虫的生命阶段很感兴趣，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.