Genetic Analysis of Mosquito Metamorphosis

蚊子变态的遗传分析

基本信息

批准号：
7692806
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
项目类别：
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/7692806
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

项目摘要

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，数以百万计的人死亡或严重衰弱，疟疾，登革热，黄热病和几种形式的病毒性脑炎。血管蚊子传递这些疾病的病因[1，2]。随着人类和蚊子种群的全球变暖和迁徙的增加，登革热可能传播到美国无登革热地区[3-8]。当前控制这些疾病的方法强调免疫，化学预防，对昆虫载体的控制以及与昆虫载体的接触减少。它们很有用，但是疾病仍然是重大问题，尤其是在不发达的热带国家[9，10]。尽管广泛使用，但对于化学载体控制剂起作用的分子机制而言，知之甚少，留下有限的选择来修改或改善这些控制方法。针对蚊子生物学的新计划正在开发中。一个倡议是发展具有降低疾病药物能力的转基因蚊子的发展[11-18]。为了实现这一目标，分子遗传技术已应用于蚊子研究。其中包括对冈比亚山脉的测序[19]，艾德斯埃及[20]和Culex pipiens Genomes [21]，开发了产生稳定的转基因蚊子[22-32]的技术[22-32]，RNAI技术的使用，RNAI技术的使用[16，33-37]，以及遗传驱动系统的开发以及遗传驱动系统的发展[24，38-41]。另外，分子遗传学技术可能揭示了化学蚊子控制剂起作用的分子机制。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形的分子遗传机制，以识别可以利用的过程，以更好地控制携带蚊子的血噬性，疾病的种群。获得的信息可能会导致设计更具体和生物理性的幼虫化学物质，并且在转基因蚊子的设计中，在其中改变了生长和变质过程，从而降低了成人人群密度或繁殖力。驱动该建议的中心假设是甲丁烯耐受剂（MET）和宽（BR）是控制变态的转录因子级联的核心，以及在商业幼虫剂中广泛使用的幼年激素类似物的途径，与变质相互作用。这里提出的是中央假设的基因检测。我们使用蚊子是因为我们发现的信息可能直接适用于蚊子种群的控制。现在可以使用这种方法，因为我们开发了用于蚊子幼虫的RNAi技术，这为我们提供了一个独特的机会，可以从遗传上检查各种基因在蚊子变质中的作用。为了进一步对我们的中心假设的遗传分析，以及对控制蚊子生长和变态的其他因素的研究，我们提议发展蚊子幼虫的体内短暂转染。蚊子传播疾病的有效控制将需要综合方法[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，而且可以传达导致致命和严重使人衰弱的药物，例如疟疾，登革热和西方脑炎。这项研究的长期目标是了解控制蚊子幼虫生长和变形的分子机制，以鉴定可以利用的潜在靶标，以更好地控制携带蚊子的疾病的血液数量。我们建议通过敲低基因表达测试，即宽阔和甲丁烯耐受性基因是蚊子发育的核心，并且在该途径中，某些杀虫剂阻止了蚊子发育。