Genetic analysis of Cryptosporidium

隐孢子虫的遗传分析

• 批准号: 8790232
• 负责人: BORIS STRIEPEN
• 金额: $ 37.25万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8790232
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Address; Africa; Age; Animal Model; Animals; Asia; Biological Assay; Cessation of life; Child; Child Mortality; Chronic; Controlled Study; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; DNA; Diarrhea; Disease; Disease Outbreaks; Electroporation; Enteral; Flow Cytometry; Gene Expression; Gene Fusion; Gene Transfer Techniques; Genes; Genetic; Genetic Vectors; Goals; Growth and Development function; HIV; Hand; Immune; Immunocompetent; Individual; Infection; Laboratories; Life; Luciferases; Malaria; Modeling; Morbidity - disease rate; Multicenter Studies; Mus; Nature; Parasites; Pathogenesis; Patients; Pharmaceutical Preparations; Plasmid Cloning Vector; Protein Biosynthesis; Protocols documentation; Reporter; Reporter Genes; Resistance; Rotavirus; Scheme; Site; Small Intestines; Sporozoites; Symptoms; System; Testing; Toxoplasma; Transfection; Transgenes; Transgenic Organisms; Translating; Viral; Work; age group; genetic analysis; homologous recombination; immunosuppressed; intestine surgery; mortality; nucleotide metabolism; parasite genome; pathogen; prevent; protein expression; public health relevance; research study; tissue culture; tool; transgene expression; waterborne

DESCRIPTION (provided by applicant): Cryptosporidium causes life threatening enteric disease in HIV-AIDS patients. Immunocompetent individuals are susceptible, but here symptoms are self-limiting. Cryptosporidium is also well known to cause diarrhea in small children. However, the full impact of Cryptosporidium on child mortality and morbidity was only recently appreciated. After rotavirus, Cryptosporidium is the most common pathogen responsible for severe diarrhea in children under 2 years. The main roadblock to achieving urgently needed advances is the overall poor tractability of Cryptosporidium in the laboratory. The goal of this project is to develop genetic tools for this parasite, and the effort builds on ou recent breakthrough in achieving transfection for C. parvum. Specifically, we will use the assay in hand to iteratively optimize transfection vectors and protocols for Cryptosporidium. We will devise strategies to select and isolate stable transgenic parasites from infected animals, and we will use these tools to establish a reporter model for Cryptosporidium. Such reporter pathogens will immediately open the disease to study and establish robust and quantitative correlates of infection, pathogenesis, drug cure, and immune-protection. In the long term, the ability to modify the parasite's genome will enable fundamental discovery and translate into tools and opportunities to treat and prevent cryptosporidiosis.

描述（由申请人提供）：隐孢子虫会导致 HIV-AIDS 患者危及生命的肠道疾病。免疫能力强的个体很容易受到影响，但症状是自限性的。众所周知，隐孢子虫还会引起小儿腹泻。然而，直到最近才认识到隐孢子虫对儿童死亡率和发病率的全面影响。继轮状病毒之后，隐孢子虫是导致 2 岁以下儿童严重腹泻的最常见病原体。实现迫切需要的进展的主要障碍是实验室中隐孢子虫的总体易处理性较差。该项目的目标是开发针对这种寄生虫的遗传工具，这项工作建立在我们最近在实现小隐孢子虫转染方面取得的突破的基础上。具体来说，我们将使用现有的测定来迭代优化隐孢子虫的转染载体和方案。我们将制定策略从受感染的动物中选择和分离稳定的转基因寄生虫，并且我们将使用这些工具建立隐孢子虫的报告模型。这些报告病原体将立即打开疾病的大门，以研究并建立感染、发病机制、药物治疗和免疫保护之间强有力的定量关联。从长远来看，修改寄生虫基因组的能力将使根本性的发现成为可能，并转化为治疗和预防隐孢子虫病的工具和机会。