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

本项目旨在了解杀菌剂影响疫霉菌病原体的作用模式。疫霉菌属于被称为卵菌的生物系统发育组。卵菌的行为类似于植物病原真菌（因此使用术语杀菌剂），并且可以作为真菌处理。马铃薯疫霉是马铃薯疫病的主要病原菌，因此寻找更有效的防治马铃薯疫病的方法具有重要的经济和环境意义。工作将包括研究目前的杀菌剂，并使用化学蛋白质组学工具来破译它们在病原体中的蛋白质目标。最初，这将通过合成各种基于已知作用模式的杀菌剂的探针来完成。我们将使用多种方法，包括将化合物开发成光亲和探针，通过蛋白质组学在活细胞中进行目标鉴定。一旦方法得到验证，我们将继续研究作用方式未知的化合物。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，从而产生一个可以挖掘新化合物的作用模式“特征”的数据集。一旦了解了各种杀菌剂的作用方式，就有可能利用收集到的新数据开发出新的更有效的杀菌剂。该项目是利兹大学（University of Leeds）和先正达集团（Syngenta Group）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.