Genetic Analysis of Cryptosporidium

隐孢子虫的遗传分析

基本信息

批准号：
9529991
负责人：
BORIS STRIEPEN
金额：
$ 34.5万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9529991
关键词：
Acquired Immunodeficiency Syndrome Address Africa Age Animal Model Animals Asia Biological Assay Cessation of life Child Child Mortality Chronic 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 Malnutrition 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 experimental study genetic analysis homologous recombination immunosuppressed intestine surgery mortality nucleotide metabolism parasite genome pathogen prevent protein expression public health relevance tissue culture tool transgene expression waterborne

项目摘要

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）：隐孢子虫引起艾滋病毒艾滋病患者生命危害生命的肠道疾病。免疫能力的个体很容易受到影响，但是这里的症状是自我限制的。众所周知，隐孢子虫会引起小孩的腹泻。但是，隐孢子虫对儿童死亡率和发病率的全部影响才受到人们的赞赏。轮状病毒后，隐孢子虫是2岁以下儿童严重腹泻的最常见病原体。迫切需要进步的主要障碍是实验室中隐孢子虫的总体障碍性不佳。该项目的目的是为这种寄生虫开发遗传工具，并且在获得C. parvum的转染方面的最新突破性基础上。具体而言，我们将手头使用该测定法对隐孢子虫的转染向量和方案进行优化。我们将制定从感染动物中选择和隔离稳定的转基因寄生虫的策略，我们将使用这些工具来建立隐孢子虫的记者模型。这种记者病原体将立即开放该疾病，以研究和建立感染，发病机理，药物治愈和免疫保护的鲁棒和定量相关性。从长远来看，修改寄生虫基因组的能力将使基本发现并转化为治疗和预防隐孢子虫病的工具和机会。