Molecular structure and function of an insect pH-sensitive chloride (pHCl) channel, a target for safer insecticides.

Insects, such as bees, play a crucial role within Earth’s intricate web of life as pollinators and are indispensable for global food security and ecosystem preservation. However, their populations are declining due to pesticide use, while pest species are becoming increasingly resistant to the synthetic compounds widely used in modern agriculture. This current situation makes it necessary to increase our understanding of insect ion channels. Therefore, our project is driven by a profound interest in the structure and pharmacological properties of a pH-sensitive chloride channel (pHCl), which is found exclusively in invertebrates. pHCl presents a potential novel target for pesticides, yet despite its significance, information about its structure and function is lacking. Consequently, the purpose of this study is to provide a comprehensive understanding of the pHCl insect ion channel, using functional and structural data. Through recombinant expression of pHCl channels in established cell lines and electrophysiological recordings, this project seeks to explore ion channel functionality and pesticide interactions. Furthermore, we aim to elucidate the molecular structure of pHCl ion channels at atomic resolution, employing cryo-EM, which would represent a landmark achievement. Ultimately, this project might inspire the development of safer pesticides to protect pollinating species and biodiversity.