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

针对成年雌性埃及伊蚊 lncRNA 的生物合理农药的开发

• 批准号: 10742558
• 负责人: Molly Duman Scheel
• 金额: $ 23.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-11 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10742558
• 关键词: Adult; Aedes; Arboviruses; Behavior; Behavioral; Biological Process; Blood; Cessation of life; Chromatin; Culicidae; Dengue; Development; Evaluation; Female; Gene Expression; Gene Silencing; Gene Targeting; Genes; Genetic; Genetic Transcription; Genome; Human; Insect Vectors; Insecta; Insecticide Resistance; Investigation; Larva; Mediating; Medical; Methods; Minor Lymphocyte Stimulatory Loci; Morphology; Mosquito Control; Oral; Pesticides; Physiological; Play; Production; RNA; RNA Interference; RNA interference screen; Reproduction; Research; Research Personnel; Role; Saccharomyces cerevisiae; Specificity; System; Testing; Transcript; Transcriptional Regulation; Untranslated RNA; Validation; Virus; Yeasts; Yellow Fever; ZIKA; arboviral disease; chikungunya; dark matter; disease transmission; disorder control; feeding; gene function; genetic manipulation; human disease; interest; life history; male; neural; new technology; novel; novel strategies; pathogen; programs; sex; sexual dimorphism; sugar; trait; transmission process; vaccine development; vaccine distribution; vector; vector control; vector mosquito

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.

项目总结 埃及伊蚊是引起寨卡病毒、基孔肯雅热、黄热病和 登革热是世界上分布最广、影响最大的虫媒病毒病。雌性蚊子不同于 雄性在形态、生理和行为特征上促进繁殖和传播 病原体。最近在A. 埃及伊蚊基因组，包括位于决定性别的M/m基因座区域的数量。这样的人很少 曾经被认为是暗物质的lncRNA基因已经得到了功能验证或表征。本研究 检验了M/m基因座区域lncRNA基因在成人中以性别特异性方式发挥作用的假设。 女性。本研究的目标包括：(1)完成基于RNAi的大规模筛查以识别 成年雌性行为或生存所需的LncRNA以及(2)这些RNAs的功能特征 通过操纵成年女性的基因表达来获得基因。追求这些目标将涉及 糖饵运送酵母的新技术的开发 文字记录水平。这项研究计划是首次对成人LncRNAs的功能特征进行研究 蚊子，将促进阐明控制蚊子的新基因靶点和开发新的 操纵这些基因表达的方法。在这次调查中采用的策略， 可应用于其他lncRNA、媒介昆虫物种和媒介生物过程的研究 重要的是，将有助于促进范式转变，这可能导致许多lncRNA的功能验证 具有重要医学价值的昆虫的基因。