Fusarium fungi that attack wheat can produce a mycotoxin, deoxynivalenol (DON), that acts as a disease virulence factors, facilitating Fusarium parasitism of wheat. DON is a protein synthesis inhibitor, and cause cell death in eukaryotes. The wheat genome has co-evolved with the Fusarium pathogen and its toxic metabolites. We have identified a range of wheat genes that are DON responsive and, in exotic wheat germplasm, most are associated with the phenotypic resistance to both DON-induced bleaching and are located within a chromosomal locus that confers resistance to both DON and Fusarium pathogens. Three of these genes have been shown to directly contribute to the DON resistance of such wheat germplasm (VIGS analysis). One is a novel, evolutionary divergent gene. These and other DON-resistance associated genes, offer potential for enhancing eukaryotic stress tolerance. Using a combination of gene overexpression/silencing studies and a range of analytical and molecular techniques, we now want to determine whether the encoded proteins can enhance biotic and abiotic stress tolerance in whole plants. Additionally, we want to characterise novel genes and associated pathways that enhance plant stress resistance.