Functional Genomics of Cryptosporidium parvum

小隐孢子虫的功能基因组学

基本信息

批准号：
7254141
负责人：
GIOVANNI WIDMER
金额：
$ 41.77万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7254141
关键词：
Acquired Immunodeficiency Syndrome Animal Model Apoptosis Applications Grants Area Biochemical Pathway Biology Bos taurus Cattle Cells Child Cryptosporidium parvum DNA DNA Microarray Chip DNA Microarray format Development Diarrhea Drug Delivery Systems Future Gene Chips Gene Expression Gene Expression Regulation Generations Genes Genetic Genetic Processes Genetic Transcription Genome Genomics Goals Human Immune response In Vitro Individual Infection Inflammation Intestines Label Life Cycle Stages Light Location Metabolic Pathway Methods Molecular Molecular Probes Molecular Profiling Mus Necrosis Numbers Oocysts Open Reading Frames Parasites Pathogenesis Pathway interactions Patients Pattern Pharmaceutical Preparations Phase Plasmodium Process Production Propionibacterium acnes Regulation Research Resources Specificity Sporozoites Staging Stimulus Symptoms Targeted Research Technology Testing Therapeutic Corynebacterium Parvum Toxoplasma gondii Transcript Validation Virulence Virus Work antimicrobial base cDNA Arrays cDNA Probes drug development excystation experience functional genomics functional group genome sequencing in vitro Model in vivo innovation pathogen response tool

项目摘要

DESCRIPTION (provided by applicant): This is a revised grant application to study global gene expression in Cryptosporidium parvum and in host cells infected with this parasite. Cryptosporidium parvum is an opportunistic pathogen in people with AIDS and is a common cause of diarrhea in children worldwide. The completed sequence of the C. parvum genome provides new opportunities for identifying drug targets and for research on this parasite on a genomic and functional level. In this project DNA microarrays will be used to study parasite gene regulation and the response of the host cell to this infection. Analysis of global parasite transcription, primarily during excystation, host cell invasion, and the initial phase of intracellular development will identify parasite biochemical pathways, which are differentially expressed during this phase of the life cycle. Analysis of the transcriptional response of infected host cells in culture and in animal models will identify mechanisms by which the host responds to the infection, and shed light on the molecular pathways leading to the intestinal symptoms of cryptosporidosis. This project is a collaborative effort between two research groups with complementary expertise in the biology and genomics of C. parvum and extensive collaborative experience. In Specific Aim 1 a comprehensive DNA microarray containing all of the genes of C. parvum will be developed. This task will take advantage of the genomic sequence by converting genomic information into a tool for identifying genetic processes associated with parasite development. In Specific Aim 2 microarrays developed under aim 1 will be used to probe global gene expression during oocyst excystation, host cell invasion, and first generation merogony. Specific Aim 3 will use commercially available human and mouse gene arrays to study the response of the host cell to C. parvum. A comparison of the host cell response to C. parvum type 1 and type 2 will be performed to probe the molecular basis of the observed difference in virulence between types.

描述（由申请人提供）：这是一份修订后的拨款申请，用于研究小隐孢子虫和感染该寄生虫的宿主细胞中的整体基因表达。小隐孢子虫是艾滋病患者的机会致病菌，也是全世界儿童腹泻的常见原因。小隐孢子虫基因组的完整序列为识别药物靶点以及在基因组和功能水平上研究这种寄生虫提供了新的机会。在这个项目中，DNA 微阵列将用于研究寄生虫基因调控和宿主细胞对此感染的反应。主要在排泄、宿主细胞入侵和细胞内发育的初始阶段对寄生虫的整体转录进行分析，将识别寄生虫的生化途径，这些途径在生命周期的这一阶段有差异表达。对培养物和动物模型中受感染宿主细胞的转录反应进行分析将确定宿主对感染做出反应的机制，并揭示导致隐孢子虫病肠道症状的分子途径。该项目是两个研究小组的合作成果，这两个研究小组在小隐孢子虫生物学和基因组学方面具有互补的专业知识和丰富的合作经验。在具体目标 1 中，将开发包含小隐孢子虫所有基因的综合 DNA 微阵列。这项任务将利用基因组序列，将基因组信息转化为识别与寄生虫发育相关的遗传过程的工具。在特定目标 2 中，目标 1 下开发的微阵列将用于探测卵囊排出、宿主细胞入侵和第一代生殖细胞发育过程中的整体基因表达。 Specific Aim 3 将使用市售的人类和小鼠基因阵列来研究宿主细胞对小隐孢子虫的反应。将比较宿主细胞对 1 型和 2 型微小隐孢子虫的反应，以探讨所观察到的类型之间毒力差异的分子基础。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Over-expression and localization of a host protein on the membrane of Cryptosporidium parvum infected epithelial cells.

DOI：
10.1016/j.molbiopara.2009.07.004
发表时间：
2009-11
期刊：
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
影响因子：
1.5
作者：
Yang, Yi-Lin;Serrano, Myrna G.;Sheoran, Abhineet S.;Manque, Patricio A.;Buck, Gregory A.;Widmer, Giovanni
通讯作者：
Widmer, Giovanni

Preferential infection of dividing cells by Cryptosporidium parvum.

小隐孢子虫优先感染分裂细胞。