Revealing the Targets and Mode of Action of Plant Fungicides Using Chemical Proteomic Tools

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This project aims to understand the mode of action by which fungicides affect pathogens belonging to the Phytophthora group. Phytophthora belong to a phylogenetic group of organisms referred to as oomycetes. Oomycetes behave similarly to phytopathogenic fungi (hence the use of term fungicide) and can be treated as fungi for the purpose of this project. Phytophthora infestans is the pathogen responsible for causing the potato blight and so it is of economic and environmental importance to find more effective ways of combatting the blight. Work will involve looking at current fungicides and using chemical proteomic tools to decipher their protein targets in the pathogen. Initially, this will be done by synthesising a variety of probes based on fungicides of known mode of action. We will use a variety of approaches, including developing compounds into photoaffinity probes for target identification in live cells by proteomics. Once methods have been validated, we will move on to compounds of unknown mode of action. We will also use quantitative proteomics to assess the impact of different fungicides on the proteome, producing a dataset that can be mined for mode of action "signatures" of novel compounds.Once the mode of action of a variety of fungicides is understood, opportunity may arise to develop new and more potent fungicides that exploit the new data gathered. This project is a joint venture between the University of Leeds, who bring expertise in chemical proteomics methodology and bioorganic chemistry, and Syngenta Group, who bring expertise in fungicidal mode of action.