Genetic Analysis of Mosquito Metamorphosis

蚊子变态的遗传分析

• 批准号: 7895740
• 负责人: James T. Nishiura
• 金额: $ 11.78万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895740
• 关键词: Adult; Aedes; Anopheles gambiae; Area; Automobile Driving; Binding; Biochemical Genetics; Biological Metamorphosis; Biology; Blood; Cells; Chemicals; Country; Culex pipiens; Culicidae; DNA Sequence; Dengue; Development; Disease; Encephalitis; Fertility; Gene Expression; Genes; Genetic; Genetic Techniques; Genetic screening method; Genome; Global Warming; Goals; Grant; Growth; Immunization; Injection of therapeutic agent; Insect Vectors; Insecticides; Investigation; Juvenile Hormones; Larva; Lead; Left; Literature; Malaria; Methods; Methoprene; Midgut; Molecular; Molecular Genetics; Mosquito Control; Mosquito-borne infectious disease; Pathway interactions; Plasmids; Play; Population; Population Control; Population Density; Process; Production; Prophylactic treatment; Proteins; RNA Interference; Reporter Genes; Reporting; Research; Role; Students; System; Techniques; Technology; Testing; Tissues; Transfection; Transgenic Organisms; United States; United States National Institutes of Health; Viral Encephalitis; Work; Yellow Fever; base; design; disorder control; gene function; genetic analysis; hormone analog; human migration; improved; in vivo; innovation; killings; knock-down; meetings; novel strategies; public health relevance; sucking; transcription factor; vector control

DESCRIPTION (provided by applicant): Yearly, millions of people die, or are seriously debilitated, from malaria, dengue fever, yellow fever and several forms of viral encephalitis. Hematophageous mosquitoes transmit the causative agents of these diseases [1, 2]. As global warming, and migration of human and mosquito populations increases, dengue fever may spread to dengue-free regions of the United States [3-8]. Current methods to control these diseases emphasize immunization, chemical prophylaxis, control of the insect vectors, and reduced contact with insect vectors. They are useful, but the diseases remain significant problems, especially in underdeveloped tropical countries [9, 10]. Although widely used, little is known concerning the molecular mechanisms by which chemical vector control agents work, leaving limited options to modify or improve these methods of control. New initiatives targeting mosquito biology are in development. One initiative is the development of transgenic mosquitoes having a reduced ability to transmit the disease agents [11-18]. In pursuit of this goal, molecular-genetic techniques have been applied to mosquito research. These include the sequencing of the Anopheles gambiae[19], Aedes aegypti [20] and Culex pipiens genomes[21], developing techniques to produce stable transgenic mosquitoes [22-32], the use of RNAi techniques [16, 33-37] and development of genetic drive systems [24, 38-41]. Additionally, molecular-genetic techniques may reveal molecular mechanisms by which chemical mosquito control agents work. Along this line, our long term goal is to understand the molecular- genetic mechanisms that control mosquito larval midgut growth and metamorphosis in order to identify processes that can be exploited to better control populations of hematophageous, disease carrying mosquitoes. The information obtained may result in the design of more specific and bio-rational larvicidal chemicals, and in the design of transgenic mosquitoes in which growth and metamorphic processes are altered so that adult population densities, or fecundity, are reduced. The central hypothesis driving this proposal is the genes methoprene tolerant (met) and broad (br) are central to the transcription factor cascade that controls metamorphosis, and in the pathway by which juvenile hormone analogues, widely used in commercial larvicides, interfere with metamorphosis. Proposed here are genetic tests of the central hypothesis. We use mosquitoes because the information we discover will likely be directly applicable to the control of mosquito populations. This approach is now possible because we have developed RNAi techniques for use in mosquito larvae, giving us a unique opportunity to genetically examine the role that various genes play in mosquito metamorphosis. To further the genetic analysis of our central hypothesis, and in investigations of other factors controlling mosquito growth and metamorphosis, we propose to develop in vivo transient transfection of mosquito larvae. Effective control of mosquito borne diseases will require an integrated approach [42] including transgenic mosquitoes, chemical control, avoidance of mosquitoes and immunization. ) PUBLIC HEALTH RELEVANCE: Mosquitoes are not just pests but can transmit the agents that cause deadly and seriously debilitating diseases such as malaria, dengue fever and westnile encephalitis. The long term goal of this research is to understand the molecular mechanisms that control mosquito larval growth and metamorphosis in order to identify potential targets that can be exploited to better control the number of blood-sucking, disease carrying mosquitoes. We propose to test, by knockdown of gene expression, the hypothesis that the genes broad and methoprene tolerant are central to mosquito development, and are in the pathway by which some insecticides block mosquito development.

描述（由申请人提供）：每年，数百万人死于疟疾、登革热、黄热病和几种形式的病毒性脑炎。食血蚊子传播这些疾病的病原体 [1, 2]。随着全球变暖以及人类和蚊子种群迁徙的增加，登革热可能会蔓延到美国无登革热的地区[3-8]。目前控制这些疾病的方法强调免疫、化学预防、控制昆虫媒介以及减少与昆虫媒介的接触。它们很有用，但这些疾病仍然是重大问题，特别是在不发达的热带国家[9, 10]。尽管广泛使用，但人们对化学病媒控制剂发挥作用的分子机制知之甚少，因此修改或改进这些控制方法的选择有限。针对蚊子生物学的新举措正在制定中。其中一项举措是开发传播疾病病原体能力降低的转基因蚊子[11-18]。为了实现这一目标，分子遗传学技术已应用于蚊子研究。其中包括冈比亚按蚊[19]、埃及伊蚊[20]和淡色库蚊基因组[21]的测序、开发生产稳定转基因蚊子的技术[22-32]、RNAi技术的使用[16, 33-37]以及遗传驱动系统的开发[24, 38-41]。此外，分子遗传学技术可能揭示化学灭蚊剂发挥作用的分子机制。沿着这条线，我们的长期目标是了解控制蚊子幼虫中肠生长和变态的分子遗传机制，以确定可用于更好地控制噬血、携带疾病的蚊子种群的过程。获得的信息可能导致设计更具体和生物合理的杀幼虫化学品，以及设计转基因蚊子，其中生长和变态过程被改变，从而降低成虫密度或繁殖力。推动这一提议的核心假设是，甲虫酯耐受基因 (met) 和宽基因 (br) 是控制变态的转录因子级联的核心，并且在广泛用于商业杀幼虫剂的保幼激素类似物干扰变态的途径中。这里提出了中心假设的基因测试。我们使用蚊子是因为我们发现的信息可能直接适用于控制蚊子种群。这种方法现在成为可能，因为我们已经开发出了用于蚊子幼虫的 RNAi 技术，为我们提供了一个独特的机会来从基因角度检查各种基因在蚊子变态中所起的作用。为了进一步对我们的中心假设进行遗传分析，并研究控制蚊子生长和变态的其他因素，我们建议开发蚊子幼虫的体内瞬时转染。有效控制蚊媒疾病需要采取综合方法[42]，包括转基因蚊子、化学控制、避免蚊子和免疫接种。 ） 公共卫生相关性：蚊子不仅是害虫，还可以传播导致致命和严重使人衰弱的疾病的病原体，例如疟疾、登革热和西尼罗脑炎。这项研究的长期目标是了解控制蚊子幼虫生长和变态的分子机制，以确定可用于更好地控制吸血、携带疾病的蚊子数量的潜在目标。我们建议通过基因表达的敲低来测试这样的假设：广泛的基因和甲虫酯耐受性是蚊子发育的核心，并且是一些杀虫剂阻止蚊子发育的途径。