Developing Tools to Study Encystation in E Histolytica

描述（由申请人提供）：原生动物寄生虫溶组织内阿米巴每年导致约5000万例侵袭性疾病，是全球第二大导致死亡的寄生虫。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，阿米巴腹泻还有显著的发病率！疾病，尤指患有营养不良和发育迟缓的儿童溶组织芽胞杆菌被列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囊体阶段的转化。这种对疾病传播至关重要的转化，目前对其了解甚少。我们的目标是开发工具来研究溶组织芽胞杆菌的发育生物学。第一个目标是建立溶组织芽胞杆菌囊肿和滋养体的全基因组转录谱。囊肿转录谱分析将使用体内囊肿和相关的脱落滋养体进行，并将提供第一个全基因组范围的囊肿和滋养体特异性基因鉴定。第二个目的是建立一种溶组织芽胞杆菌体外溶胞的方法。我们将利用易成囊的溶组织芽胞杆菌菌株，在模拟结肠环境的条件下培养它们，并将它们暴露在导致相关系统成囊的刺激下。体外环化的成功发展将使我们能够解剖这种寄生虫发育生物学的关键方面，包括确定触发环化的途径。这些方法有望为溶组织芽胞杆菌的分化提供初步见解，并为进一步表征这种寄生虫的发育程序铺平道路。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水净化系统受到不利影响的任何地方引起感染。海啸或区域政治和社会基础设施动荡等事件可能导致疾病出现。我们感兴趣的是了解寄生虫的生命阶段，以确定诊断、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.