Developing High-throughput screens for pesticides targeting insect ion channels

害虫给加拿大农业造成了数十亿美元的损失。尽管最近在抗虫害的转基因植物方面取得了进展，但农药仍然是农民防止作物损失和破产的最重要的防御手段。然而，现有农药的未来受到害虫抗性演变和对现有农药对环境和人类健康影响的担忧的威胁。通过研究果蝇的生理，我们对昆虫的生理有了更好的了解，并确定了我们认为是开发下一代杀虫剂的有价值的新靶点。我们发现昆虫使用离子通道CG7589来调节分泌和消化。CG7589通道对果蝇的生存能力至关重要，因此干扰该通道功能的农药将是致命的。由于CG7589通道仅存在于昆虫及其相关生物（螨虫、蜱虫等）中，因此专门针对该通道的农药不会对人类或其他有益（非节肢动物）生物造成伤害。最后，由于没有现有的农药靶向CG7589，对其他农药具有抗性的生物不太可能对靶向CG7589的农药产生抗性。我们这个项目的目标是开发找到这种杀虫剂的工具。这将涉及在培养的细胞系中表达CG7589，使通道具有功能但不伤害细胞，并且可以使用电压敏感染料监测通道的活性，记录CG7589对细胞生理学的影响。当我们开发出这样的细胞系后，我们将进行一个试点药物筛选，看看我们是否可以用它来识别潜在的杀虫剂。

Insect pests cause billions of dollars of damage to Canadian agriculture. In spite of recent advances in pest-resistant genetically modified plants (GMOs), pesticides continue to be the most important defense farmers have against crop loss and insolvency. However, the future of current pesticides is threatened by the evolution of resistance in pests and concerns about the impact of existing pesticides on the environment and on human health. By studying the physiology of the fruit fly, we have come to a better understanding of the insect physiology and identified what we believe to be a valuable new target for the development of the next generation of pesticides. We found that insects use an ion channel, CG7589, to regulate secretion and digestion. The CG7589 channel is essential to the viability of the fruit fly and therefore a pesticide that interferes with the channel's function will be lethal. Because the CG7589 channel is only found insects and related organisms (mites, ticks etc.), a pesticide specifically targeting the channel will not harm humans or other beneficial (non-arthropod) organisms. Finally, because no existing pesticide targets CG7589, organisms that are resistant to other pesticides are unlikely to be resistant to a pesticide targeting CG7589. Our goal in this project is to develop the tools to find such a pesticide. That will involve expressing CG7589 in a cultured cell line such that the channel is functional but does not harm the cells and so that the activity of the channel can be monitored using voltage-sensitive dyes that record the effects of CG7589 on cell physiology. When we have developed such a cell line, we will perform a pilot drug screen to see whether we can use it to identify potential pesticides.