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

本项目旨在了解杀真菌剂影响疫霉属病原体的作用方式。疫霉属属于被称为卵菌的生物体的系统发育组。卵菌的行为类似于植物病原真菌（因此使用术语杀真菌剂），并可作为本项目目的的真菌处理。致病疫霉是引起马铃薯枯萎病的病原体，因此找到更有效的防治枯萎病的方法具有经济和环境重要性。这项工作将涉及研究目前的杀菌剂，并使用化学蛋白质组学工具来破译病原体中的蛋白质靶点。最初，这将通过基于已知作用模式的杀真菌剂合成各种探针来完成。我们将使用各种方法，包括将化合物开发成光亲和探针，用于通过蛋白质组学在活细胞中进行靶点识别。一旦方法得到验证，我们将继续研究未知作用模式的化合物。我们还将使用定量蛋白质组学来评估不同杀菌剂对蛋白质组的影响，产生一个数据集，可以挖掘新化合物的作用模式“签名”。一旦了解了各种杀菌剂的作用模式，就有机会开发新的和更有效的杀菌剂，利用收集的新数据。该项目是利兹大学和先正达集团的合资项目，前者带来了化学蛋白质组学方法和生物有机化学方面的专业知识，后者带来了杀真菌作用模式方面的专业知识。

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.