GENETIC CONTROL OF FILARIAE DEVELOPMENT IN MOSQUITOES

丝状线虫Wuchereria bancrofti、Brgia Malayi和B.Timori 淋巴丝虫病是由蚊子传播的病原体引起的吗 大约8000万人分布在热带地区和副主题，其中 另有7.5亿人面临风险。控制努力一直在进行 蚊子出现杀虫剂抗药性严重受阻 人口，对农药应用的环境担忧，缺乏 疫苗开发的进展，以及现有疫苗的有限阵列 用于预防或治疗的药理药物。终极的 本研究的目的是在基因水平上确定 影响蚊虫对丝虫病媒介能力的因素 并利用这些信息开发新的控制策略，旨在 破坏蚊媒丝虫病的生命周期。这项研究 描述主要研究蚊子埃及伊蚊及其基因 与丝虫、马来丝虫作为模式系统的关系 阐明遗传控制机制，因为丰富的知识 关于这种载体的遗传学的现有资料。此外，还有一些 所提议的研究的方面包括W.Bancrofti的主要载体， 致倦库蚊。本项目的具体目标是(1) 利用基于图谱的方法分离影响丝虫易感性的基因 克隆技术，(2)分离与之密切相关的分子 对丝虫敏感或耐药的蚊子品系 体内氨基酸标记和差异显示聚合酶链式反应研究进展 方法学，(3)获得可诱导免疫多肽的DNA克隆， Ae.中鉴定的多肽。埃及人通过合作努力 与分子和细胞生物学研究所的一个研究小组合作， (4)构建了CX的RFLP连锁图谱。P。 Ququiefasciatus，使用先前为Ae.埃及伊蚊，以及 使用此地图来识别这些标记与 影响Cx易感性/不应性的基因。P。 Ququiefasciatus对马来丝虫发育的影响，以及(5)评估 候选基因，在特定目标1-4中确定，以正或 对丝状线虫的发育产生负面影响 Sindbis或AeDNV病毒表达系统与科罗拉多州合作 州立大学。

The filarioid nematodes Wuchereria bancrofti, Brugia malayi, and B. timori are mosquito-transmitted pathogens responsible for lymphatic filariasis in approximately 80 million humans throughout the tropics and subtopics, with an additional 750 million people at risk. Control efforts have been seriously hampered by emergence of pesticide resistance in mosquito populations, environmental concerns over pesticide applications, lack of progress in vaccine development, and the limited array of available pharmacological agents for prophylaxis or treatment. The ultimate objective of this research is to determine, at the genetic level, those factors that influence the vector competence of mosquitoes for filarial worms and to use this information to develop novel control strategies aimed at disrupting the life cycle of mosquito-borne filariasis. The research described primarily examines the mosquito, Aedes aegypti, and its genetic relationship with the filarial worm, B. malayi, as a model system for elucidating genetic control mechanisms, because of the wealth of knowledge available concerning the genetics of this vector. Additionally, some aspects of the proposed research include a primary vector for W. bancrofti, Culex pipiens quinquefasciatus. The specific aims of this project are (1) isolate genes that influence filarial worm susceptibility using map-based cloning techniques, (2) isolate molecules that are tightly associated with mosquito strains that are susceptible or refractory to filarial worm development using in vivo amino acid labeling and differential display PCR methodologies, (3) obtain DNA clones of inducible immune peptides and polypeptides identified from Ae. aegypti through a collaborative effort with a research group at the Institute of Molecular and Cellular Biology, Strasbourg, France, (4) construct a RFLP linkage map of Cx. p. quinquefasciatus, using markers developed previously for Ae. aegypti, and use this map to identify linkage associations between these markers and the genes that influence susceptibility/refractoriness of Cx. p. quinquefasciatus to B. malayi development, and (5) assess the potential of candidate genes, identified in specific aims 1-4, to positively or negatively influence the development of filaroid nematodes using the Sindbis or AeDNV virus expression systems in cooperation with Colorado State university.