Investigation and characterisation of diamide insecticide resistance conferred by target-site mutations in the ryanodine receptor of lepidopteran pest

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Diamide insecticides, such as flubendiamide and chlorantraniliprole, act as conformation sensitive activators of insect ryanodine receptors (RyR), releasing calcium from intracellular stores in insect muscle, and causing an irreversible paralysis. These compounds are the main active ingredients in diamide formulations used to control a diverse range of herbivorous insects, particularly lepidopterans such as the diamondback moth, Plutella xylostella, a notorious global pest on cruciferous crops. This common pest has recently developed widespread resistance to diamides through specific mutations in the trans-membrane domain of the RyR. Additional diamide insecticides such as cyclaniliprole, broflanilide and tetraniliprole are currently under development and will further increase the selection pressure on a number of target pests. It is therefore a key priority to investigate these resistance mechanisms by means of detailed biochemical and molecular studies. This project will characterise their impact on diamide insecticide action and RyR function, using state of the art approaches including cell-line expression of recombinant proteins, radioligand binding studies, electrophysiological recordings, calcium imaging and CRISPR/Cas9 guided drosophila transgenesis, and will be key to providing a fundamental understanding of diamide insecticide binding to allelic RyR variants. This knowledge will further impact future resistance management strategies for diamides and the discovery pipeline for novel insecticidal RyR modulators. You will be trained in standard biochemical, molecular and genetic techniques that are widely applicable and will also benefit from learning more specialised techniques such as insect transgenesis. You will also be required to spend 3 months on placement with the industry partner Bayer CropScience in Monheim, Germany.