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.

项目摘要 蚊子传播疾病在大多数发展中国家代表了主要健康问题，并且 出现是发达国家流行病暴发的重大威胁。加剧这些 问题是蚊子种群中杀虫剂耐药性的出现，耐药性 在寄生虫种群中，疫苗开发的进展延迟，缺乏支持 蚊子控制计划，并增加了全球旅行。 Culex Pipiens复合物中的蚊子 是淋巴丝虫类线虫寄生虫，Wuchereria Bancrofti和几个的主要向量 arboviruses。其中包括最近引入的北美西尼罗河病毒。长期 拟议研究的术语目标是识别，隔离和表征遗传因素 与隔离相关，这种特征强烈影响地理分布和生存 Culex Pipiens复合物中的物种。目前，没有关于分子的知识 culex中的渗水的决定因素。该提案的目标是基于一般的 可以通过鉴定和隔离与肿瘤表型相关的基因的假设 位置克隆技术。确定确定滞育和知识的基因 从对相关生化途径的详细理解可以有几个 潜在应用，包括：促进限制和疾病限制的转基因结构 人口替代后的行为，靶向生物农药的发展或 鉴定生物学相关的拮抗剂，破坏对病原体至关重要的行为 传播或生存。该项目的具体目的是：1）精细的地图基因组区域 确定为确定抑郁表型的基因，2）识别候选基因 确定滞育和3）对确定滞育的候选基因进行功能分析。 来自遗传十字的信息将用于CX。 Quinquefasciatus基因组 项目以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分析以确认和扩展 有希望的基因的微阵列结果。阳性候选基因将用于生物学 使用RNA干扰介导的基因敲低或使用基因过表达相关性 重组sindbis转导病毒。然后，实验实验的结果将是 在代表CX的天然种群中进行评估。 Pipiens S.S.和CX。 Quinquefasciatus。