DEFENSIN GENE REGULATION AND MOSQUITO VECTOR COMPETENCE

描述（改编自申请人的摘要）：防御素是 埃及伊蚊应答微生物产生的优势免疫肽 越来越多的数据表明，这种分子，无论是单独使用，还是 与其他免疫因子协同作用，可干扰 蠕虫和疟疾寄生虫，如果防御素基因在早期被诱导， 感染为了解决防御素和免疫球蛋白的整体假设， 蚊子的抗微生物体液反应可以限制 真核寄生虫，提出了以下具体目标：（1）识别 并描述了这些机制调节防御素的基因表达， AE.埃及伊蚊的长期目标是确定寄生虫如何能够 避免开启这种免疫反应;（2）评估防御素的生物学 关于其时空表达模式， 原始免疫记忆系统的存在，以及它们杀死 体外和体内真核寄生虫;（3）使用可用的序列数据 免疫肽在伊蚊和按蚊开始隔离 和表征库蚊中的免疫肽，并确定是否免疫 激活限制了班氏吴氏杆菌在该天然载体中的发育; 和（4）使用转导病毒和转座子介导的转化， 批判性地评价防御素和/或其它免疫肽 杀死蠕虫和疟疾寄生虫。埃及和Cx. pipiens。 研究Cx。Pipiens和W. bancrofti是可能的，因为 与埃及研究人员的合作安排。

DESCRIPTION (Adapted from the Applicant's Abstract): Defensins are the predominant immune peptide produced by Aedes aegypti in response to microbial insult, and a growing amount of data suggest this molecule, either alone or in concert with other immune factors, can interfere with the development of filarial worms and malaria parasites, if the defensin gene is induced early in an infection. To address the overall hypothesis that defensins and the antimicrobial humoral response of mosquitoes can limit the development of eukaryotic parasites, the following specific aims are proposed: (1) To identify and characterize those mechanisms regulating gene expression of defensins in Ae. Aegypti, with the long-term goal of determining how parasites are able to avoid turning on this immune response; (2) to evaluate the biology of defensins regarding their temporal and spatial expression patterns, the potential existence of a primitive immunological memory system, and their ability to kill eukaryotic parasites in vitro and in vivo; (3) to use sequence data available for immune peptides in Aedes and Anopheles mosquitoes to begin the isolation and characterization of immune peptides in Culex and to determine if immune activation limits the development of Wucheria bancrofti in this natural vector; and, (4) to use transducing viruses and transposon-mediated transformation to critically evaluate the ability of defensins and/or other immune peptides to kill filarial worms and malaria parasites in Ae. aegypti and Cx. pipiens. Studies with Cx. Pipiens and W. bancrofti are possible because of a collaborative arrangement with researchers in Egypt.