GUT-SPECIFIC GENES OF SIMULIUM

SIMULIUM 的肠道特异性基因

• 批准号: 3146491
• 负责人: MARCELO JACOBS-LORENA
• 金额: $ 17.75万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3146491
• 关键词: Drosophilidae; Simuliidae; arthropod borne communicable disease; communicable disease control; complementary DNA; gastrointestinal epithelium; gel electrophoresis; gene expression; gene induction /repression; genetic manipulation; genetic mapping; genetic promoter element; genetic regulation; high performance liquid chromatography; host organism interaction; immunological substance; in situ hybridization; insect control; life cycle; molecular cloning; molecular genetics; nucleic acid probes; nucleic acid sequence; onchocerciasis; protozoal antigen; regulatory gene; structural genes; Drosophilidae; Simuliidae; arthropod borne communicable disease; communicable disease control; complementary DNA; gastrointestinal epithelium; gel electrophoresis; gene expression; gene induction /repression; genetic manipulation; genetic mapping; genetic promoter element; genetic regulation; high performance liquid chromatography; host organism interaction; immunological substance; in situ hybridization; insect control; life cycle; molecular cloning; molecular genetics; nucleic acid probes; nucleic acid sequence; onchocerciasis; protozoal antigen; regulatory gene; structural genes

In spite of its importance as a potential target for disease control, the insect gut has received little attention. Insect-borne parasites of human disease frequently initiate their development in the insect by penetrating its gut. The gut of hematophagous insects is also the site of blood digestion, a process that triggers egg production and ultimately influences insect fitness and reproduction. This proposal is to develop molecular approaches for the study of the Simulium gut, focusing on the above-mentioned processes. Simulium (blackfly) is the vector for onchocerciasis (river blindness), a debilitating disease that affects millions of people in Africa and Latin America. The parasite is ingested by the blackfly with the blood meal from an infected individual. In order to develop, the parasite must penetrate the blackfly gut. Penetration is largely but not entirely hindered by the secretion by the gut epithelium of a thick peritrophic matrix (PM) that surrounds the blood meal. There are reasons to believe that inhibition of PM formation would result in excessive parasite burden which causes fly lethality. One goal of the proposed research is to clone the genes encoding the two major PM components. The structural organization of these genes, including essential promoter elements, Will be defined and factors required for the gut-specific regulation of gene expression will be investigated. A second focus of this research is the investigation of genes which function in the digestion of the blood meal. Two genes which were previously isolated in this laboratory and encode putative proteolytic enzymes, will be similarly characterized. Finally, antibodies to Simulium gut proteins will be produced and used to explore the feasibility of developing immunological approaches to alter the fitness of the fly or to modify its vector capacity. The ultimate goal of these experiments is to provide the means for devising rational approaches of vector and disease control.

尽管它是作为疾病的潜在目标的重要性 控制，昆虫的肠道很少受到关注。 昆虫传播 人类疾病的寄生虫经常在 昆虫通过穿透其肠道。 血虫昆虫的肠道也是 血液消化的部位，该过程触发鸡蛋的产生和 最终影响昆虫的健身和繁殖。 该提议是 为了开发分子方法来研究Simulium肠道， 专注于上述过程。 Simulium（Blackfly）是chocerciasis的矢量（河流 失明），一种令人衰弱的疾病，影响数百万的人 非洲和拉丁美洲。 寄生虫被黑蝇摄入 感染者的血液餐。 为了发展， 寄生虫必须穿透黑蝇肠道。 穿透主要是 完全受到浓密的肠道上皮的分泌所阻碍 围绕血液粉的营养性基质（PM）。 有原因 相信抑制PM形成会导致过度 寄生虫负担会导致苍蝇致死。 拟议的目标之一 研究是克隆编码两个主要PM组件的基因。 这 这些基因的结构组织，包括基本启动子 元素将被定义和肠道特异性所需的因素 将研究基因表达的调节。 第二个重点 这项研究是对在 消化血餐。 以前在 该实验室和编码推定的蛋白水解酶将是 类似地表征。 最后，对仿真肠道蛋白的抗体 将生产并用来探索开发的可行性 免疫学方法改变​​苍蝇的适应性或修改苍蝇 向量容量。 这些实验的最终目标是提供 设计媒介和疾病控制理性方法的手段。