The development of biorational pesticides targeting lncRNAs in adult female Aedes aegypti mosquitoes

项目摘要 埃及伊蚊是引起寨卡病毒、基孔肯雅病毒、黄热病和 登革热是世界上最广泛和最重要的虫媒病毒疾病。雌性蚊子与 男性在形态，生理和行为特征，促进生殖和传播 病原体最近在A. 埃及伊蚊基因组，包括一些存在于性别决定的M/m基因座区域。几个这样 lncRNA基因，曾经被认为是暗物质，已经在功能上得到验证或表征。本研究 检验了M/m位点区域lncRNA基因在成年人中以性别特异性方式发挥功能的假设。 女性本研究的目的包括：（1）完成基于RNAi的大规模筛选， 成年女性行为或生存能力所需的lncRNA和（2）这些lncRNA的功能表征 通过操纵成年女性的基因表达来控制基因。为实现这些目标， 开发了能够操纵lncRNA的酵母糖诱饵递送新技术 转录水平。这项研究计划，第一个研究功能特点lncRNAs在成人 蚊子，将促进阐明新的基因目标，以控制蚊子和发展新的 操纵这些基因表达的方法。在这次调查中采用的策略， 本研究可应用于其它lncRNA、媒介昆虫种类及媒介生物学过程的研究 重要性，将有助于促进范式转变，可能导致许多lncRNA的功能验证 昆虫中的重要医学基因。

PROJECT SUMMARY Aedes aegypti is the primary mosquito vector of viruses that cause Zika, chikungunya, yellow fever, and dengue, the most widespread and significant arboviral disease in the world. Female mosquitoes differ from males in morphological, physiological, and behavioral traits that facilitate reproduction and the transmission of pathogens. Thousands of putative long non-coding RNA (lncRNA) genes were recently identified in the A. aegypti genome, including a number that reside in the sex-determining M/m locus region. Few of these lncRNA genes, once considered dark matter, have been functionally validated or characterized. This study examines the hypothesis that M/m locus region lncRNA genes function in a sex-specific manner in adult females. The aims of this study include: (1) completion of an RNAi-based large-scale screen to identify lncRNAs that are required for adult female behavior or viability and (2) characterization of the function of these genes through manipulation of gene expression in adult females. Pursuit of these aims will involve the development of novel technology for sugar-baited delivery of yeast that enables manipulation of lncRNA transcript levels. This research program, the first study to functionally characterize lncRNAs in adult mosquitoes, will promote the elucidation of new gene targets for mosquito control and the development of new methods to manipulate the expression of these genes. The strategies employed in this investigation, which could be applied to the study of other lncRNAs, vector insect species, and biological processes of vector importance, will help promote a paradigm shift that may result in the functional validation of many lncRNA genes in insects of medical importance.