Our research hypothesis is that the current strategy of selecting biocontrol strains against fungal plant pathogens is fundamentally flawed, because often based on a single mode-of-action and assessed on artificial media. Hence, high potential strains in vitro frequently perform inconsistently once tested under ecological relevant conditions. In this project we have selected a specific set of actinobacteria to control Fusarium graminearum in wheat. F. graminearum is the main causal agent of fusarium head blight, causing a reduction in yield. Moreover, its toxic metabolites called mycotoxins pose a risk for human and animal health. These actinobacterial strains were obtained using an innovative screening methodology in which they were tested in relevant natural ecological niches such as wheat leaves, stubble and ears. This uncharted biocontrol potential is the premise for present project. We will implement this carefully chosen set of strains at critical stages of the F. graminearum life cycle: growth, reproduction, mycotoxin biosynthesis. We will uncover the molecular mechanisms involved in this cross kingdom communication (actinobacteria vs Fusarium). A detailed knowledge of the mechanisms involved will allow us to expand the applicability of these strains towards a broader spectrum of pathogens. In view of a sustainable implementation of our biocontrol tool, we will investigate the impact on the residing microbiome and other pathogens of wheat in the field using mesocosms.