DETOXPEST · Towards increased biosafety for non-target insects - Damage-activated proteolysis to selectively enhance toxicity of pesticides

Insects numbers and diversity have rapidly declined in the EU and worldwide. Pesticides, and particularly the toxicity of insecticides to non-target insects (e.g. bees), are one of the major drivers of insect declines. Apart from destabilizing natural ecosystems, pollinator disappearance directly threatens food security.To help combat insect decline, I propose an innovative approach for the damage-activation of pro-pesticides (DAPP) by plant proteases that are activated in the gut of feeding caterpillars. Non-target beneficial insects that cause no damage, including pollinators and natural enemies of pests, are spared. My team pioneers the study of proteolysis in the plant wound response, following our recent discovery that physical damage activates a class of proteases, called metacaspases. I hypothesize that i) damage-activated plant proteolysis is a largely unrecognized but potential key player in the plant wound response to insect herbivores and ii) this knowledge can be used to enhance pesticide biosafety. We will study the impact of fall armyworm (Spodoptera frugiperda), an invasive insect pest and potential major threat to EU agriculture, on the model plant Arabidopsis thaliana and the economically important crop maize. A combination of advanced (N-terminomics) and novel (Proteome Integral Solubility Alteration) proteomics technologies will allow us to uncover unknown plant metacaspase substrates and damage-activated proteases and to assess their impact on insect herbivory. These fundamental studies will feed information into a pipeline of first-in-class DAPP development, where we will modify biological insecticides with newly-discovered protease cleavage sites. Finally, we will test toxicity against target (Spodoptera) and non-target insects. My early-stage and fundamental research on damage-activated proteolysis can have a tremendous positive impact on the increase of insecticide selectivity to help combat the escalating problem of insect decline.