Unravelling the molecular determinants of insecticide sensitivity in the Hymenoptera HYMOTOX

Hymenoptera (sawflies, wasps, ants, and bees) are an environmentally and economically important order of insects that carry out vital ecosystem services in their role as parasitoids, predators, and pollinators. However, while performing this function, hymenopteran species may come into contact with potentially harmful xenobiotics in the environment such as pesticides. We have recently demonstrated that the impact of pesticides on the health of managed bee species is profoundly influenced by the capacity of a small group of cytochrome P450 enzymes (P450s) to convert these compounds to less toxic forms. However, for the vast majority of the >150,000 hymenopteran species the role of these enzymes as determinants of insecticide sensitivity remains unknown. The overarching objective of the HYMOTOX project is to address this critical knowledge gap by exploiting the natural diversity within the Hymenoptera, in combination with new advances in genomics, synthetic biology and protein modelling, to understand how variation in these biotransformation enzymes across an entire order of insects impacts sensitivity to pesticides. Our analyses will establish the extent to which insecticide-detoxifying P450s are shared across hymenopteran diversity, identify critical structural and functional determinants of P450-mediated insecticide metabolism, and develop a framework for predicting hymenopteran sensitivity to insecticides based on genomic information.The project will progress beyond the state of the art by providing: i) a step-change advance in our understanding of the molecular determinants of insecticide sensitivity in the Hymenoptera, ii) a new paradigm for pesticide risk assessment that moves beyond the use of data derived from a few managed model species, iii) powerful knowledge, tools and resources that can be used to predict and avoid negative pesticide-insect interactions and in the development of next-generation insecticides that are safe to beneficial insects.