Diapause in Culex Mosquitoes

库蚊滞育

• 批准号: 8278677
• 负责人: DAVID W SEVERSON
• 金额: $ 59.71万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278677
• 关键词: Address; Adult; Arboviruses; Area; Behavior; Biochemical Pathway; Biological Assay; Biology; Candidate Disease Gene; Climate; Complex; Culex (Genus); Culex pipiens; Culicidae; Data Analyses; Developed Countries; Developing Countries; Development; Diapause; Disease; Disease Outbreaks; Drug resistance; Engineering; Epidemic; Experimental Designs; Female; Filaria bancrofti; Filarial Elephantiases; Foundations; Gene Expression Profile; Gene Expression Regulation; Genes; Genetic; Genetic Crosses; Genetic Markers; Genetic Transcription; Genome; Genome Mappings; Genomics; Geographic Distribution; Goals; Health; Human; Individual; Insecticide Resistance; Knowledge; Laboratories; Lymphatic; Mediating; Microarray Analysis; Microsatellite Repeats; Molecular; Molecular Genetics; Molecular Profiling; Mosquito Control; Mosquito-borne infectious disease; Nematoda; North America; Parasites; Pattern; Phenotype; Population; Population Replacements; Procedures; Production; Protocols documentation; Quantitative Trait Loci; RNA Interference; Recombinants; Relative (related person); Research; Restriction fragment length polymorphism; Single Nucleotide Polymorphism; Single-Stranded Conformational Polymorphism; Surveys; Techniques; Time; Transgenes; Travel; Vaccines; Validation; Virus; West Nile virus; base; disease transmission; disorder control; disorder prevention; genome sequencing; genome-wide; novel; overexpression; pathogen; positional cloning; programs; research study; trait; transmission process; vaccine development; vector

Project Summary Mosquito-borne diseases represent major health problems in most developing countries and have emerged as significant threats for epidemic outbreaks in developed countries. Exacerbating these problems are the emergence of insecticide resistance in mosquito populations, drug resistance among parasite populations, delayed progress in vaccine development, lack of support for mosquito control programs, and increased global travel. Mosquitoes in the Culex pipiens complex are primary vectors for the lymphatic filarioid nematode parasite, Wuchereria bancrofti and several arboviruses. This includes the recently introduced West Nile virus in North America. The long- term objectives of the proposed research are to identify, isolate and characterize genetic factors associated with diapause, a trait that strongly impacts the geographic distribution and survival of species within the Culex pipiens complex. At present, no knowledge exists on the molecular determinants of diapause in Culex. The objectives of this proposal are based on the general hypothesis that genes associated with the diapause phenotype can be identified and isolated by positional cloning techniques. Identification of genes determining diapause and the knowledge from the detailed understanding of the associated biochemical pathways could have several potential applications including: transgene constructs that promote altered and disease limiting behaviors following population replacement, development of targeted biopesticides, or identification of biologically relevant antagonists that disrupt behaviors critical to pathogen transmission or survival. The specific aims of the project are to: 1) fine-scale map genome regions identified as containing genes that determine the diapause phenotype, 2) identify candidate genes determining diapause, and 3) conduct functional analysis of candidate genes determining diapause. Information from genetic crosses will be leveraged against the Cx. quinquefasciatus genome project to identify candidate genes within discrete genome regions. Candidate genes will be evaluated using microarrays, followed by quantitative real time PCR assays to confirm and expand microarray results for promising genes. Positive candidate genes will be assayed for biological relevance using RNA interference mediated gene knockdowns or gene overexpression using recombinant Sindbis transducing viruses. Results from laboratory experiments will then be evaluated among natural populations representing Cx. pipiens s.s. and Cx. quinquefasciatus.

项目概要 蚊媒疾病是大多数发展中国家的主要健康问题，并且已 已成为发达国家流行病爆发的重大威胁。加剧这些 问题是蚊子种群中出现杀虫剂抗药性、耐药性 在寄生虫种群中，疫苗开发进展缓慢，缺乏支持 蚊子控制计划，以及增加全球旅行。淡色库蚊复合体中的蚊子 是淋巴丝状线虫寄生虫、班氏乌切菌和几种的主要载体 虫媒病毒。这包括最近在北美引入的西尼罗河病毒。长- 拟议研究的长期目标是识别、分离和表征遗传因素 与滞育有关，这是一种强烈影响地理分布和生存的特征 淡色库蚊复合体内的物种。目前，尚无关于分子的知识。 库蚊滞育的决定因素。本提案的目标基于总体 假设与滞育表型相关的基因可以通过以下方法鉴定和分离 定位克隆技术。确定滞育基因的鉴定和知识 从对相关生化途径的详细了解中可以得出以下几个结论： 潜在的应用包括：促进改变和限制疾病的转基因构建体 人口更替后的行为、针对性生物农药的开发，或 鉴定破坏对病原体至关重要的行为的生物学相关拮抗剂 传播或生存。该项目的具体目标是：1）精细绘制基因组区域图 鉴定为含有决定滞育表型的基因，2) 鉴定候选基因 确定滞育，以及3)对确定滞育的候选基因进行功能分析。 来自遗传杂交的信息将被用来对抗 Cx。致带五线虫基因组 项目旨在识别离散基因组区域内的候选基因。候选基因将是 使用微阵列进行评估，然后进行定量实时 PCR 测定以确认和扩展 有前景基因的微阵列结果。阳性候选基因将进行生物学检测 使用 RNA 干扰介导的基因敲低或基因过度表达的相关性 重组辛德比斯转导病毒。实验室实验的结果将是 在代表 Cx 的自然群体中进行评估。皮皮安斯公司和Cx。致倦五线虫。