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.

项目摘要 埃及埃及是导致Zika，Chikungunya，黄热病和 登革热是世界上最普遍，最严重的丁香病毒疾病。雌性蚊子不同 男性在形态，生理和行为特征方面有助于繁殖和传播 病原体。最近在A中鉴定出数千个推定的长非编码RNA（LNCRNA）基因。 埃及基因组，包括一个存在于性别确定的m/m基因座区域中的数字。其中很少 曾经被认为是暗物质的lncRNA基因已在功能上验证或表征。这项研究 检查了M/M基因座区域lncRNA基因在成人中以性别特异性起作用的假设 女性。这项研究的目的包括：（1）完成基于RNAi的大规模屏幕以识别 成人女性行为或生存力所需的LNCRNA以及（2）这些功能的表征 通过操纵成年女性基因表达的基因。追求这些目标将涉及 开发新型技术，用于糖诱导的酵母输送，以操纵lncrna 成绩单级别。该研究计划是第一个在功能上表征成人LNCRNA的研究 蚊子将促进蚊子控制的新基因靶标和新基因的发展 操纵这些基因表达的方法。这项调查中采用的策略 可以应用于其他LNCRNA，载体昆虫物种和载体的生物学过程 重要性将有助于促进范式转变，这可能导致许多LNCRNA的功能验证 具有医学重要性的昆虫的基因。