GENETIC CONTROL OF FILARIAE DEVELOPMENT IN MOSQUITOES

蚊子丝虫发育的基因控制

• 批准号: 6458995
• 负责人: BRUCE MARTIN CHRISTENSEN
• 金额: $ 31.28万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6458995
• 关键词: Aedes; Culicidae; Filarioidae; Sindbis virus; Wuchereria; arthropod borne communicable disease; artificial chromosomes; chromosome walking; disease /disorder model; disease /disorder proneness /risk; disease vectors; gene expression; gene induction /repression; genetic markers; genetic regulation; genetic strain; gerbil /jird; host organism interaction; linkage mapping; messenger RNA; molecular cloning; polymerase chain reaction

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.

丝状线虫：Wuchereria bancrofti、Brugia malayi 和 B. timori 蚊子传播的病原体是导致淋巴丝虫病的原因吗 热带地区和亚热带地区约有 8000 万人，其中 另有 7.5 亿人处于危险之中。 控制力度已 蚊子对杀虫剂产生抗药性的出现严重阻碍了这一进程 人口、对农药使用的环境问题、缺乏 疫苗开发的进展以及可用的疫苗种类有限 用于预防或治疗的药物。 终极 这项研究的目的是在基因水平上确定那些 影响蚊媒丝虫能力的因素 蠕虫并利用这些信息来制定新的控制策略，旨在 破坏蚊媒丝虫病的生命周期。 研究 描述的主要检查蚊子，埃及伊蚊，及其遗传 与丝虫 B. malayi 的关系，作为模型系统 由于知识丰富，阐明了遗传控制机制 有关该载体的遗传学的信息。 此外，一些 拟议研究的各个方面包括 W. bancrofti 的主要载体， 致倦库蚊。 该项目的具体目标是（1） 使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）分离与紧密相关的分子 对丝虫敏感或耐药的蚊种 使用体内氨基酸标记和差异显示 PCR 进行开发 方法学，(3)获得诱导性免疫肽的DNA克隆和 从Ae中鉴定出的多肽。埃及伊蚊通过共同努力 与分子和细胞生物学研究所的一个研究小组， 法国斯特拉斯堡 (4) 构建了 Cx 的 RFLP 连锁图。 p。 quinquefasciatus，使用之前为 Ae 开发的标记。埃及伊蚊，和 使用此图来识别这些标记与 影响 Cx 的易感性/不应性的基因。 p。 quinquefasciatus 到 B. malayi 的发展，以及 (5) 评估 在特定目标 1-4 中确定的候选基因，以积极或 使用该方法对丝状线虫的发育产生负面影响 与科罗拉多州合作的 Sindbis 或 AeDNV 病毒表达系统 州立大学。