Functional Genemics of Cryptosporidium parvum

小隐孢子虫的功能基因组学

• 批准号: 7086882
• 负责人: GIOVANNI WIDMER
• 金额: $ 43.04万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7086882
• 关键词: Cryptosporidium; biotechnology; cow; cryptosporidiosis; functional /structural genomics; gene expression; host organism interaction; immature animal; laboratory mouse; microarray technology; nucleic acid sequence; parasitism; protozoal genetics; swine

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）：这是修订的赠款应用程序，用于研究隐孢子虫中的全球基因表达以及感染该寄生虫的宿主细胞中。隐孢子虫是艾滋病患者的机会性病原体，是全球儿童腹泻的常见原因。 C. parvum基因组的完整序列为鉴定药物靶标和研究该寄生虫的研究提供了新的机会。在这个项目中，DNA微阵列将用于研究寄生虫基因调节以及宿主细胞对该感染的反应。分析全球寄生虫转录，主要是在ExcyStation，宿主细胞侵袭和细胞内发育的初始阶段的分析将识别寄生虫生化途径，这些途径在生命周期的这一阶段差异表达。分析感染宿主细胞在培养物和动物模型中的转录反应将确定宿主对感染反应的机制，并阐明导致隐孢子虫病的肠道症状的分子途径。该项目是两个研究小组之间的合作努力，这些研究小组在C. parvum的生物学和基因组学和广泛的协作经验方面具有互补的专业知识。 在特定的目标1中，将开发包含所有Parvum基因的全面DNA微阵列。该任务将通过将基因组信息转换为用于识别与寄生虫发育相关的遗传过程的工具来利用基因组序列。在特定的目标中，AIM 1开发的微阵列将用于探测卵囊脱离，宿主细胞侵袭和第一代Merogony期间的全局基因表达。特定的目标3将使用市售的人类和小鼠基因阵列来研究宿主细胞对C. parvum的响应。将进行对宿主细胞对1型孢子梭菌和2型的宿主细胞反应的比较，以探测类型之间观察到的毒力差异的分子基础。