阿维菌素类药剂在世界范围内广泛应用于节肢动物害虫和寄生性线虫的防治，其最重要的生理靶标是谷氨酸门控氯离子通道。目前，已报道该通道基因突变与阿维菌素类抗药性相关，但阿维菌素的受体位点和点突变的抗性贡献及其对种群适合度的影响尚不明确。本项目拟利用全球性为害十字花科蔬菜、对阿维菌素已产生高水平抗性的小菜蛾为试虫，利用模型驱动的对接分析，预测潜在受体位点（Q253、S294、N298、P302、A309和G315）突变介导的通道变构效应，通过卵母细胞表达和电生理实验明确目标位点的药理学特性，并采用CRISPR/Cas9技术在小菜蛾基因组中对候选位点进行编辑，测定其对阿维菌素毒力和种群适合度的影响。本项目将在分子、细胞和个体水平对阿维菌素靶向谷氨酸门控氯离子通道的受体位点进行模拟对接、功能验证和综合解析，研究结果将为小菜蛾等有害生物的抗性监测和治理提供科学依据，为阿维菌素类新型药剂研发奠定理论基础。

Avermectins are widely used as one of the most effective control measures in the globe fight against arthropod pests and parasitic nematodes. Glutamate-gated chloride channels (GluCl) are the major targets for avermectins. Previous studies identified several mutations associated with abamectin/ivermectin resistance. However, the receptor sites for abamectin on GluCls, the contribution to abamectin resistance of single mutation, and effects on fitness of the genomic-edited strains remain elusive. The diamondback moth, Plutella xylostella, is one of the most devastating insect pests of cruciferous vegetables around the world, and lots of field populations have evolved high levels of resistance to abamectin. In this study, we will make use of 3D model-driven mutagenesis to predict the allosteric effects resulted from potential receptor residues mutation occurring at Q253, S294, N298, P302, A309 and G315 of GluCl channel of P. xylostella. We will also employ the Xenopus oocytes expression system and electrophysiology to confirm the pharmacological response to abamectin of the candidate residues, which might be involves in receptor sites. Furthermore, in order to clear whether the above six mutations will results in abamectin-resistant phenotype and fitness cost in P. xylostella, the CRISPR/Cas9 mediated genomic-editing will be performed subsequently. This study will mapping the receptor sites for abamectin on PxGluCl channel, by synthetically analyzing the molecular docking, two-electrode voltage clamp recording and genomic-editing results obtains in molecular, cellular and individual levels, respectively. Results from this work could facilitate implementing effective resistance monitoring and management strategies in the diamondback moth and other arthropod pests, as well as provide target model for novel avermectins development.