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严重腹泻的最重要原因之一 这种疾病在美国的流行病学各不相同。 疫情的爆发与娱乐用水和饮用水受污染有关，并且大规模发生 因艾滋病毒/艾滋病、器官移植或其他原因而遭受免疫抑制的患者。 癌症对全球公共卫生的影响甚至更大：仅次于轮状病毒。 隐孢子虫是幼儿和婴儿中最重要的腹泻病原体。 特别是在营养不良的情况下，隐孢子虫病对 儿童早期总体死亡率和发病率也与发育迟缓有关。 没有疫苗，只有单一药物，给儿童的未来留下了持久的阴影。 这种寄生虫具有单一宿主生命周期，包括无性和有性过程。 依次发生在同一宿主的肠上皮中，完成这一发育过程。 对于持续感染、严重疾病和病原体传播，需要制定计划。 药物和疫苗开发生命周期的明显重要性，我们当前的 这是一种非常复杂的生物现象。 这里有很多值得发现的地方——我们期待对基础和转化的见解 我们最近开创了一个隐孢子虫遗传系统，我们将使用它。 这个项目将在分子和细胞水平上剖析生命周期。 开发严格的分子标记和检测方法，以促进无性和有性的发育 阶段，揭示阶段特定基因表达，并发现执行功能的机制 缺乏有效的隐孢子虫培养系统。 我们将明确体外开发的具体脱轨之处，以及 这些见解将指导未来的工作，以促进持续的文化模型。