Genetic Analysis of Mosquito Metamorphosis

蚊子变态的遗传分析

• 批准号: 8289516
• 负责人: James T. Nishiura
• 金额: $ 11.66万
• 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 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8289516
• 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; 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(申请人提供)：每年有数百万人死于疟疾、登革热、黄热病和几种形式的病毒性脑炎，或严重虚弱。嗜血性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，登革热可能会传播到美国的非登革热地区[3-8]。目前控制这些疾病的方法强调免疫、化学预防、控制病媒和减少与病媒的接触。它们是有用的，但这些疾病仍然是严重的问题，特别是在欠发达的热带国家[9，10]。虽然被广泛使用，但人们对化学媒介控制剂的作用分子机制知之甚少，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开发中。一项倡议是开发转基因蚊子，使其传播病原体的能力降低[11-18]。为了实现这一目标，分子遗传学技术已被应用到蚊子研究中。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，开发生产稳定的转基因蚊子的技术[22-32]，使用RNAi技术[16，33-37]和开发遗传驱动系统[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学机制，以便确定可以利用的过程，以更好地控制携带疾病的嗜血性蚊子的数量。所获得的信息可能导致设计更具体和生物合理的杀幼虫药物，以及设计转基因蚊子，在这些蚊子中，生长和变质过程被改变，以降低成虫密度或繁殖力。支持这一提议的中心假设是，耐甲氧丁二烯(MET)和广谱(BR)基因是控制变态的转录因子级联的中心，也是广泛用于商业杀幼虫的保幼激素类似物干扰变态的途径。这里提出的是对中心假说的基因测试。我们使用蚊子是因为我们发现的信息很可能直接适用于控制蚊子种群。这种方法现在是可能的，因为我们已经开发出用于蚊子幼虫的RNAi技术，这给了我们一个独特的机会来从遗传学上研究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学分析，并在研究控制蚊子生长和变态的其他因素方面，我们建议开展体内瞬时转基因蚊子幼虫的研究。有效控制蚊媒疾病将需要一种综合方法[42]，包括转基因蚊子、化学控制、避免蚊子和免疫接种。) 与公共卫生相关：蚊子不仅是害虫，还可以传播导致疟疾、登革热和西部脑炎等致命和严重衰弱疾病的病原体。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，以便确定可以利用的潜在靶点，以更好地控制吸血、携带疾病的蚊子的数量。我们建议通过基因表达的敲除来检验这样的假设，即广泛的和耐甲氧丁二烯的基因是蚊子发育的中心，并且处于一些杀虫剂阻止蚊子发育的途径中。