A Chemical Proteomic Workflow for Rapid Identification of Proteins Responsible for Metabolic Insecticide Resistance

用于快速鉴定负责代谢杀虫剂抗性的蛋白质的化学蛋白质组工作流程

• 批准号: 2279874
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2279874
• 关键词: Chemical; Proteomic; Workflow; Rapid; Identification

Metabolic resistance is commonly a result of either elevated expression of detoxifying enzymes (e.g. cytochrome P450s) or a shift in substrate specificity in those enzymes leading to an increased capacity to detoxify insecticide(s). The responsible enzyme(s) can often not be identified rapidly since insects encode >100 detoxification enzymes. We hypothesize that a chemical proteomic approach can accelerate candidate gene/protein identification. This project aims to investigate insecticide based probe molecules to identify enzymes involved in metabolic resistance by comparing photoaffinity labeling (PAL), activity based protein profiling (ABPP) and drug affinity responsive target stability (DARTS) profiling. The elucidation of resistance mechanisms will support hypothesis based-design of next generation molecules which are not affected by this resistance mechanism.

代谢抗性通常是解毒酶（如细胞色素p450）表达升高或这些酶的底物特异性变化导致解毒能力增加的结果。由于昆虫编码100多种解毒酶，通常无法快速鉴定出负责解毒的酶。我们假设化学蛋白质组学方法可以加速候选基因/蛋白质的鉴定。本项目旨在通过比较光亲和标记（PAL）、基于活性的蛋白谱（ABPP）和药物亲和响应靶标稳定性（DARTS）谱，研究基于杀虫剂的探针分子，以鉴定参与代谢抗性的酶。抗性机制的阐明将支持基于假设的不受该抗性机制影响的下一代分子的设计。