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引起严重腹泻的最重要原因之一。 这种疾病在世界各地以不同的流行病学表现出来。在美国 疫情与受污染的娱乐和饮用水有关，并在 比例。因艾滋病毒/艾滋病、器官移植或 癌症处于最严重的危险之中。对全球公共卫生的影响更大：在轮状病毒之后， 隐孢子虫是儿童腹泻最主要的病原体。在婴儿中，在 尤其是在营养不良的背景下，隐孢子虫病对 总体儿童早期死亡率和发病率。隐孢子虫病也与发育迟缓有关，因此 给孩子们的未来留下了持久的阴影。没有疫苗，只有一种药物 具有边际效力的。这种寄生虫只有一个寄主生命周期，既有无性过程，也有有性过程 在同一宿主的肠道上皮细胞中按顺序发生。完成此开发项目 对于持续感染、严重疾病和病原体的传播，需要规划。尽管 生命周期对于药物和疫苗开发的明显重要性，我们目前 理解是最基本的。这是一种复杂得令人着迷的生物现象-- 在这里有很多值得探索的地方，我们期待着对基础知识和翻译知识的深入了解 意义。我们最近率先开发了一种隐孢子虫的基因系统，我们将在 这个项目是为了在分子和细胞水平上剖析生命周期。根据这项提议，我们将 开发用于无性和有性发育的严格分子标记和分析 阶段，揭示阶段特定的基因表达，并发现执行功能的机制 以及在生命周期中的进步。缺乏有效的培养隐孢子虫的系统 这一进程长期受阻。我们将明确在体外发育的哪些方面脱轨，以及 这些见解将指导未来的工作，以促进持续的文化模式。