Sexual Development of Cryptosporidium

隐孢子虫的性发育

• 批准号: 9529998
• 负责人: BORIS STRIEPEN
• 金额: $ 19.5万
• 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 2021-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9529998
• 关键词: AIDS/HIV problem; Alpha Cell; Antibodies; Benchmarking; Biological Assay; Biological Phenomena; Biology; Candidate Disease Gene; Cells; Cellular biology; Child; Complex; Consequences of HIV; Cryptosporidiosis; Cryptosporidium; Data; Development; Disease; Disease Outbreaks; Electron Microscopy; Epidemiology; Epithelial Cells; Event; Female; Fertilization; Future; Gametogenesis; Gene Expression; Genes; Genetic; Genetic Transcription; 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; drinking water; drug development; early childhood; fascinate; imprint; in vivo; insight; intestinal epithelium; male; 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.

隐孢子虫是引起严重腹泻的最重要原因之一