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

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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.