Molecular basis of pyrethroid resistance

超出所提供的空间。这项研究的长期目标是了解昆虫对杀虫剂抗性的分子基础。蟑螂、蚊子等害虫是人类病原体的载体，对人类健康构成重大威胁。此外，蟑螂是室内过敏原的主要来源，也是急性哮喘的一个原因。大量使用拟除虫菊酯杀虫剂来控制这些害虫，导致了抗性害虫种群的快速选择。抗性的产生是有效防治害虫的主要障碍。拟除虫菊酯的靶点钠通道蛋白的突变是拟除虫菊酯抗性的主要原因，导致对所有拟除虫菊酯杀虫剂产生交叉抗性。对天然发生的拟除虫菊酯抗性相关的钠通道突变和选择性剪接变异的分析表明，钠通道跨膜螺旋4（$4）和6（$6）在拟除虫菊酯抗性中的关键作用。然而，这些突变如何赋予拟除虫菊酯抗性尚不清楚。本研究要检验的中心工作假设是，拟除虫菊酯抗性突变要么影响拟除虫菊酯与$6中一个假定位点的结合，要么促进$4/$6在通道失活期间向静息状态移动，而这一过程被拟除虫菊酯抑制。结合分子遗传学、电生理学和药理学方法，通过分析自然和实验室产生的突变，在机制水平上了解拟除虫菊酯的作用/耐药性。具体目标是：1。拟除虫菊酯抗性突变对拟除虫菊酯与蜚蠊钠通道结合影响的研究。2. 拟除虫菊酯抗性突变对蜚蠊钠通道门控动力学影响的表征。3. 第4和第6跨膜段在拟除虫菊酯抗性中的作用的综合研究。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. The long-term goal of this research is to understand the molecular basis of insecticide resistance in insects. As carriers of human pathogens, insect pests, such as cockroaches and mosquitoes, are major threats to human health. In addition, cockroaches are a major source of indoor allergens and a cause of acute asthma. The intensive use of pyrethroid insecticides to control these pests has led to rapid selection of resistant pest populations. The development of resistance presents a major obstacle to the effective control of insect pests. Mutations in the sodium channel protein, the target of pyrethroids, are a major cause of pyrethroid resistance, resulting in cross-resistance to all pyrethroid insecticides. Analysis of naturally occurring pyrethroid resistance-associated sodium channel mutations and alternative splicing variants suggests a critical role of sodium channel transmembrane helixes 4 ($4) and 6 ($6) in pyrethroid resistance. However, how these mutations confer pyrethroid resistance is not understood. The central working hypothesis to be examined in this research is that pyrethroid-resistance mutations either affect pyrethorid binding to a putative site in $6, and/or facilitate the movement of $4/$6 to the resting state during channel deactivation, which is inhibited by pyrethroids. A combination of molecular genetic, electrophysiological and pharmacological approaches will be used to understand pyrethroid action/resistance at the mechanistic level by analyzing both natural and laboratory-created mutations. The specific aims are: 1. Examination of the effect of pyrethroid resistance mutations on pyrethroid binding to cockroach sodium channels. 2. Characterization of the effect of pyrethroid resistance mutations on cockroach sodium channel gating kinetics. 3. Comprehensive examination of the role of the 4th and 6th transmembrane segments in pyrethroid resistance. PERFORMANCE SITE ========================================Section End===========================================