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.

Filarioid nematodes Wuchereria Bancrofti，Brugia Malayi和B. Timori 蚊子传播的病原体是负责淋巴丝虫病的病原体 在整个热带和子主题中，大约有8000万人类 又有7.5亿人处于危险之中。 控制工作已经 由于蚊子中的农药耐药性而严重阻碍 人口，对农药应用的环境问题，缺乏 疫苗开发的进展以及可用的有限阵列 预防或治疗的药理剂。 最终 这项研究的目的是在遗传水平上确定 影响蚊子对媒介的矢量能力的因素 蠕虫并使用这些信息来制定针对的新颖控制策略 破坏蚊子传播丝虫病的生命周期。 研究 描述的主要检查蚊子，埃及埃及及其遗传 与丝状蠕虫B. Malayi的关系，作为模型系统 阐明遗传控制机制，因为知识丰富 有关该载体的遗传学的可用。 另外，有些 拟议研究的各个方面包括W. Bancrofti的主要向量， Culex pipiens quinquefasciatus。 该项目的具体目的是（1） 使用基于地图的孤立基因影响丝状蠕虫敏感性 克隆技术，（2）与与之紧密相关的分离分子 易感或难治性丝虫蠕虫的蚊子菌株 使用体内氨基酸标记和差分显示PCR开发 方法论，（3）获得可诱导免疫肽和的DNA克隆 从AE鉴定的多肽。通过合作的努力 在分子和细胞生物学研究所的研究小组中， 法国Strasbourg，（4）构建CX的RFLP链接图。 p。 Quinquefasciatus，使用先前为AE开发的标记。埃及，然后 使用此地图来识别这些标记与 影响CX的敏感性/折磨性的基因。 p。 Quinquefasciatus to B. Malayi开发，（5）评估的潜力 在特定目标1-4中确定的候选基因，以积极或 负面影响丝类线虫的发展 Sindbis或AEDNV病毒表达系统与科罗拉多州合作 州立大学。