Sex separation through targeting of conserved female-specific lethal genes in disease vector mosquitoes

通过针对病媒蚊子中保守的雌性特异性致死基因进行性别分离

基本信息

批准号：
10369644
负责人：
Molly Duman Scheel
金额：
$ 19.81万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-11 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369644
关键词：
Aedes Anopheles gambiae Arboviruses Behavioral Blood Chromosomes Consumption Culex (Genus)Culicidae Data Dengue Development Developmental Gene Disease Disease Vectors Evaluation Evolution Feeding behaviors Female Filarial Elephantiases Gene Targeting Genes Genetic Human Investigation Laboratories Larva Lethal Genes Malaria Mediating Methodology Methods Minor Lymphocyte Stimulatory Loci Morphology Mosquito Control Organism Orthologous Gene Outcome Partner in relationship Physiological Production Protocols documentation RNA Research Sex Chromosomes Sex Preselection Small Interfering RNA Sorting - Cell Movement Testing Translating West Nile virus X Chromosome Yeasts base feeding gene discovery gene function genetic approach human disease insight life history male novel pathogen population based programs prospective protocol development screening sex sex determination sexual dimorphism small hairpin RNA trait vector vector control vector mosquito

项目摘要

Project Summary Female mosquitoes differ from males in morphological, physiological, and behavioral traits that promote the spread of disease-causing pathogens. Although the majority of genes that regulate sexually dimorphic development in mosquitoes have not yet been identified, these genes may represent novel targets for mosquito control. Characterization of female-specific developmental genes could also elucidate genetic strategies for production and sorting of male mosquitoes, an obstacle that hinders global implementation of several emerging population-based mosquito control strategies that are dependent on mass releases of males. Clusters of loci that cause sex-specific lethal effects are believed to reside within the sex-determining M/m locus region of the dengue vector mosquito Aedes aegypti, but the identities of these genes were not previously known. A recent high-throughput RNAi-mediated screen uncovered female-specific larval lethal genes in the A. aegypti sex-determining locus region, including several genes with known orthologs in other species of disease vector mosquitoes. Yeast interfering RNA larvicides that target these genes kill female A. aegypti larvae during development, but do not impact male mosquitoes. The proposed research program will test the hypothesis, which is supported by preliminary data, that orthologs of these genes also function as female-specific larval lethal loci in Aedes albopictus (vector of multiple arboviruses), Anopheles gambiae (malaria vector), and Culex quinquefasciatus (West Nile and lymphatic filariasis vector). Specific aims of the proposed investigation include i) RNAi-mediated screening of prospective female-specific lethal genes in these disease vector mosquitoes, ii) construction and down-selection of female-specific yeast larvicides to target the genes in each species, and iii) development of protocols for yeast larvicide-based mass rearing of fit, mating- competitive male mosquitoes of all three species. It is anticipated that these studies will generate novel female-specific larvicidal control strategies, provide insight into the evolution of mosquito sex chromosomes and sex-specification mechanisms, and elucidate methodology for mass rearing of males that will facilitate emerging population-based control strategies in multiple species of human disease vector mosquitoes.

项目摘要女性蚊子在促进的形态，生理和行为特征方面与男性不同致病病原体的传播。虽然大多数调节性二态的基因尚未确定蚊子的发展，这些基因可能代表蚊子控制。女性特异性发育基因的表征也可以阐明遗传男性蚊子的生产和分类策略，这是阻碍全球实施的障碍几种基于人群的新兴蚊子控制策略取决于男性的大规模释放。据信引起性别特异性致死作用的基因座集群存在于性别确定的M/M 登革热蚊子埃及埃及的基因座区域，但这些基因的身份不是以前知道。最近的高通量RNAi介导的屏幕未发现的女性特异性幼虫致死 A. aegypti性别确定的基因座区域中的基因，包括几个具有已知直系同源物的基因疾病媒介蚊子的种类。酵母干扰靶向这些基因的RNA幼虫剂杀死雌性。埃及幼虫在发育过程中，但不会影响男性蚊子。拟议的研究计划将测试由初步数据支持的假设，即这些基因的直系同源物也起作用雌性特异性幼虫致死位点（多个arboviruses的载体），冈比亚的亚细胞病毒的载体（疟疾载体）和Culex Quinquefasciatus（西尼罗河和淋巴丝虫病载体）。特定目标拟议的研究包括i）RNAi介导的前瞻性女性特异性致死基因的筛选疾病载体蚊子，ii）雌性特异性酵母菌的结构和下调以靶向每个物种中的基因，以及iii）开发基于酵母菌幼虫的质量饲养的方案，交配 - 这三种物种的竞争性男性蚊子。预计这些研究将产生新颖女性特异性的幼虫控制策略，可深入了解蚊子性染色体的演变和性别规格机制，以及阐明雄性大规模饲养的方法论在人类疾病媒介蚊子多种物种中，新兴人群的控制策略。