Maternally transmitted symbionts, such as Wolbachia, spread through populations of their animal host by inducing cytoplasmic incompatibility (CI). CI is a powerful drive system that comes at a significant cost to the host. However, conflict theory predicts that hosts evolve suppressor systems to counteract Wolbachia-mediated costs. Although vital for our understanding of these symbiotic interactions and their societal applications, the underpinning molecular-genetic mechanisms are poorly understood. To address these gaps, I will take advantage of the imminent genetic models, Tetranychus urticae and T. cinnabarinus, that are naturally infected with CI-inducing Wolbachia. This project is innovative because it will unravel the molecular basis of CI from both the symbiont and host perspective, an ambitious but feasible objective because of recently established proof-of-concepts. The functional importance of novel CI candidate genes of Wolbachia will be validated by combining Drosophila transgenesis and Tetranychus introgression. I will track the cellular distribution and transmission of Wolbachia effectors using state-of-the-art cytology. To dissect host suppression, I will combine deep phenotyping with high-resolution genetic mapping. Functionality of candidate suppressors will be characterized by reverse genetic tools, including targeted mutagenesis. My proposal will significantly advance our mechanistic understanding of reproductive symbiosis, a pervasive phenomenon in nature.