Diapause in Culex Mosquitoes

库蚊滞育

• 批准号: 8076324
• 负责人: DAVID W SEVERSON
• 金额: $ 59.84万
• 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/8076324
• 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; 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

DESCRIPTION (provided by applicant): 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 application 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. PUBLIC HEALTH RELEVANCE: Mosquitoes in the Culex pipiens complex are primary vectors for human lymphatic filariasis and several arboviruses, including the West Nile virus. No vaccines are available and disease prevention is largely dependent on avoiding contact with infected mosquitoes. The proposed research will provide valuable new information on the biology of the mosquito relating to the ability of adult females to survive temperate climate winter in a diapause state.

描述（由申请人提供）：蚊子传播的疾病代表了大多数发展中国家的主要健康问题，并且已成为发达国家流行病爆发的重大威胁。加剧这些问题的是蚊子种群中杀虫剂耐药性的出现，寄生虫种群中的耐药性，疫苗开发的进展延迟，对蚊子控制程序缺乏支持以及增加全球旅行。 Culex Pipiens络合物中的蚊子是淋巴丝虫类线虫寄生虫，Wuchereria bancrofti和几种Arboviruses的主要载体。其中包括最近引入的北美西尼罗河病毒。拟议研究的长期目标是识别，隔离和表征与糖尿病相关的遗传因素，这一特征强烈影响了Culex Pipiens复合物中物种的地理分布和存活。目前，尚无关于culex中滞育的分子决定因素的知识。该应用程序的目标是基于一般假设，即可以通过位置克隆技术鉴定和隔离与滞育表型相关的基因。确定确定滞留的基因以及对相关生化途径的详细理解的知识可能具有多种潜在的应用，包括：促进人口替代后促进改变和疾病限制行为的转基因构建体，靶向生物农药的发展或对生物学相关的拮抗剂的识别，这些行为破坏了对病原体传播至关重要的行为。该项目的具体目的是：1）鉴定为确定基因确定抑郁表型的基因，2）识别确定抑郁的候选基因的基因，以及3）确定确定抑郁的候选基因的候选基因。来自遗传十字的信息将用于CX。 Quinquefasciatus基因组项目旨在鉴定离散基因组区域内的候选基因。将使用微阵列评估候选基因，然后进行定量实时PCR分析，以确认和扩展有前途基因的微阵列结果。利用RNA干扰介导的基因敲低或使用重组sindbis转导病毒的基因过表达的阳性候选基因将用于生物学相关性。然后，将在代表CX的天然种群中评估实验室实验的结果。 Pipiens S.S.和CX。 Quinquefasciatus。公共卫生相关性：Culex Pipiens综合体中的蚊子是人类淋巴丝虫病和包括西尼罗河病毒在内的几种Arbovires的主要媒介。没有可用的疫苗，预防疾病在很大程度上取决于避免接触被感染的蚊子。拟议的研究将提供有关蚊子生物学的有价值的新信息，该信息与成年女性在隔离状态下在温带气候冬季生存的能力有关。