Project summary
High-resolution structural analyses of human Slo3 and CatSper channels will be performed in this project, using advanced cryo-EM and cryo-ET technologies. The aim is to determine the structure of the Slo3 channel by single-particle cryo-EM. In contrast, the structure of CatSper will be determined directly within the sperm flagellum using in situ cryo-ET. The goal is to identify inhibitor-binding sites and elucidate their mechanisms of action. This work will optimise docking, molecular dynamics, and screening approaches and support structure-based, AI-assisted drug design. High-resolution structural elucidation will advance the development of novel inhibitors and lead compounds for contraceptive agents.
We established a heterologous cell culture system for the expression and purification of the human Slo3 ion channel. The purified channel is analysed using state-of-the-art cryo-electron microscopy to determine its three-dimensional structure, providing a foundation for structure-based rational drug design.
