Sexual Development of Cryptosporidium

隐孢子虫的性发育

• 批准号: 10054148
• 负责人: BORIS STRIEPEN
• 金额: $ 37.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-06-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054148
• 关键词: AIDS/HIV problem; Antibodies; Benchmarking; Biological Assay; Biological Phenomena; Biology; Candidate Disease Gene; Cells; Cellular biology; Child; Complex; Consequences of HIV; Cryptosporidiosis; Cryptosporidium; Data; Development; Diarrhea; Disease; Disease Outbreaks; Electron Microscopy; Epidemiology; Epithelial Cells; Event; Female; Fertilization; Future; Gametogenesis; Gene Expression; Gene Expression Profiling; Genes; Genetic; Germ Cells; Gold; Growth; Hour; Immunosuppression; In Vitro; Infant; Infection; Life Cycle Stages; Link; Malignant Neoplasms; Malnutrition; Meiosis; Modeling; Molecular; Morbidity - disease rate; Nature; Nutritional; Organ Transplantation; Parasites; Patients; Pharmaceutical Preparations; Phase; Process; Public Health; Reagent; Reporter; Reporter Genes; Reproduction spores; Resistance; Rotavirus; Sexual Development; Syndrome; System; Transgenic Organisms; Vaccines; Water; Work; asexual; assay development; base; chlorination; diarrheal disease; drinking water; drug development; early childhood; fascinate; imprint; in vivo; insight; intestinal epithelium; molecular marker; mortality; pathogen; programs; sex; tissue culture; transcription factor; vaccine development

The protozoan parasite Cryptosporidium is one of the most important causes of severe diarrheal disease, and the disease manifests itself with varied epidemiology around the world. In the U.S. outbreaks are linked to tainted recreational and drinking water and have occurred at massive scale. Patients suffering from immunosuppression due to HIV/AIDS, organ transplantation, or cancer are in gravest danger. The global public health impact is even larger: after Rotavirus, Cryptosporidium is the most important diarrheal pathogen in small children. In infants, in particular in the context of malnutrition, cryptosporidiosis has a highly significant imprint on overall early childhood mortality and morbidity. Cryptosporidiosis is also linked to stunting, thus leaving a lasting shadow on the future of children. There are no vaccines and only a single drug of marginal efficacy. This parasite has a single host life cycle, both asexual and sexual processes occur sequentially in the intestinal epithelium of the same host. Completion of this developmental program is required for continued infection, severe disease, and spread of the pathogen. Despite the obvious importance of the lifecycle for drug and vaccine development, our current understanding is rudimentary. This is a biological phenomenon of fascinating complexity – there is much to discover here – and we expect insights of fundamental as well as translational significance. We have recently pioneered a genetic system for Cryptosporidum that we will use in this project to dissect the lifecycle at the molecular and cellular level. Under this proposal we will develop rigorous molecular markers and assays for development through asexual and sexual stages, reveal stage specific gene expression, and discover the mechanisms that execute function and progression through the lifecycle. Lack of efficient systems to culture Cryptosporidium has long hampered progress. We will define where specifically in vitro development derails, and these insights will guide future work to facilitate a continuous culture model.

原生动物寄生虫隐孢子虫是造成转机的最重要原因之一 疾病，该疾病在美国各地表现出不同的流行病学。 Outbeaks与受污染的休闲和饮用水有关，并且发生了大规模 尺度。 癌症处于最严重的危险中。 隐孢子虫是婴儿中最重要的腹泻病原体 特别是在营养不良的背景下，隐孢子虫病具有高度显着的烙印。 总体幼儿怀孕和病态。 在儿童的未来中留下持久的阴影。 边缘疗效。 依次发生在同一宿主的肠上皮中。 持续感染，严重疾病和病原体的扩散需要程序。 生命周期对药物和疫苗开发的显而易见的重要性，我们当前 理解是基本的。 在这里发现很多东西 - 我们期望基本和翻译的见解 重要性。 该项目是在分子和细胞水平上剖析生命周期的项目。 通过无性和性开发严格的分子标记和开发测定法 阶段，启用阶段特定基因表达并发现执行功能的机制 进步剧院的生命周期缺乏有效的系统属于隐孢子虫已经拥有的系统。 长期阻碍了进度。 这些见解将指导未来的工作，以促进连续的文化模型。