Genetic Analysis of Cryptosporidium

隐孢子虫的遗传分析

基本信息

批准号：
9897477
负责人：
BORIS STRIEPEN
金额：
$ 39.34万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9897477
关键词：
Ablation Academia Acquired Immunodeficiency Syndrome Actins Age Apical Back Binding Biogenesis Biological Assay Bioterrorism Brush Border CRISPR/Cas technology Categories Cells Child Childhood Chronic Disease Clinical Trials Collaborations Cryptosporidiosis Cryptosporidium Cryptosporidium parvum DNA Defect Diarrhea Disease Disease Outbreaks Electroporation Enterocytes Epitopes Essential Genes Gene Expression Genes Goals Growth Hour Immune Immune Evasion Immune response Immunocompromised Host In Vitro Industry Injections Isotopes Kinetics Knock-out Label Life Link Measures Mediating Modernization Molecular Molecular Genetics Mus Mutagenesis Opportunistic Infections Organelles Parasites Parasitic infection Pathogenesis Pharmaceutical Preparations Positioning Attribute Predisposition Protein Export Pathway Proteins Proteome Proteomics Race Reagent Reporter Genes Resistance Role Series Site System Testing Transfection Transgenic Organisms Translational Research Ursidae Family Video Microscopy Water Work arm base burden of illness chlorination conditional mutant diarrheal disease drug candidate drug discovery functional genomics genetic analysis in vivo mortality pathogen polymerization protein function rhoptry success tool

项目摘要

Cryptosporidium is an apicomplexan parasite and one of the most important causes of severe diarrheal disease. More than 50% of U.S. outbreaks linked to water use are caused by Cryptosporidium and the parasite is thus considered a category B potential bioterrorism agent. Immunosuppressed patients are extremely susceptible and suffer life-threatening chronic disease, cryptosporidiosis is an original AIDS defining opportunistic infections. Globally, children under the age of two bear the main disease burden and Cryptosporidium is the second most important diarrheal pathogen in this group. Over the initial period of support we developed stable transformation, a series of reporter genes and CRISPR-Cas9 mediated gene knock out. We apply and further hone these new tools to investigate how this intracellular parasite manipulates its host cell. Cryptosporidium thrives in a uniquely remodeled cellular niche cells that is critical to pathogenesis, drug susceptibility and immune interaction. Our central hypothesis is that the parasite injects proteins directly into host enterocytes and that those proteins are the mechanistic effectors of invasion, remodeling and immune evasion. We have discovered the first set of such factors in C. parvum. This application will use an array of modern approaches to define the parasite's exported proteome and to understand the function of effector proteins to first establish and then maintain parasite infection.

隐孢子虫是一种Apicomplexan寄生虫，也是严重腹泻的最重要原因之一疾病。与用水有关的美国暴发中有50％以上是由隐孢子虫和因此，寄生虫被认为是B类潜在的生物恐怖剂。免疫抑制的患者是隐孢子虫病是一种原始的艾滋病定义机会性感染。在全球范围内，两岁以下的儿童承担主要疾病负担隐孢子虫是该组中第二重要的腹泻病原体。超过初始支持时期我们开发了稳定的转型，一系列记者基因和CRISPR-CAS9 介导的基因淘汰。我们应用并进一步磨练这些新工具，以研究这种细胞内如何寄生虫操纵其宿主细胞。隐孢子虫在独特的重塑细胞细胞中繁衍生息这对于发病机理，药物敏感性和免疫相互作用至关重要。我们的中心假设是寄生虫将蛋白质直接注入宿主肠上皮细胞，这些蛋白是机械入侵，重塑和免疫逃避的效果因子。我们发现了第一组此类因素 C. Parvum。该应用程序将使用一系列现代方法来定义寄生虫的导出蛋白质组并了解效应蛋白的功能首先建立然后保持寄生虫感染。