Insect cell-based screening of bioactive peptides for receptor interference

The annual economic losses to agriculture by the hundreds of major arthropod pests are estimated to exceed $120 billion in the U.S. alone. If economic impacts on human health, the environment, and other non-target arthropods are included, losses will be even more. The discovery of new insecticides to improve pest management is a long iterative process with high risk and low chances of success.




Insect neuropeptides (NPs) and their G protein-coupled receptors (GPCRs) have long been proposed as promising biological targets for the development of next-generation insecticides due to their central roles in essential biological processes. However, a key roadblock to success has been how expensive chemistries can be efficiently screened for identifying active ingredients.




Advanced genomic and proteomic tools have enabled the development of new approaches to insecticide discovery. We developed a novel GPCR-based screening platform that utilizes millions of short peptides generated by bacteriophages, combined with an insect cell expression system. These short peptides, acting as agonists or antagonist, can interfere with the target GPCR. This mechanism is called 'Receptor interference' (Receptor-i). The Receptor-i offers several key advantages: 1) rapid identification of target-specific GPCR agonists or antagonists using insect cell-based screening; 2) flexible delivery options for bioactive peptides, including topical application, ingestion, or plant-incorporated systems; and (3) a variety of GPCR targets, minimizing the development of potential insecticide resistance. This proof-of-concept technology is adaptable to a wide variety of GPCRs in other animal pest species.