The Peptide-GPCR Project

Matching all C. elegans peptide-GPCRs to their cognate neuropeptide ligands

Neuropeptides represent the largest and most diverse group of neuromodulatory substances in the nervous system, with over 350 bioactive peptides predicted in C. elegans. Most of them are thought to activate G protein-coupled receptors (GPCRs), modulating neural circuits that drive adaptive behaviors and many physiological processes. Of the roughly 100 peptide GPCRs predicted in the C. elegans genome, only a few have been deorphaned, i.e. their functionally activating peptide ligands are known.

We – the Schoofs and Beets labs – have set up the Peptide-GPCR project: a large-scale deorphanization initiative that aims at matching all predicted peptide GPCRs to their cognate neuropeptide ligands. The project’s goal is to characterize novel neuropeptide-GPCR couples and GPCR affinity using reverse pharmacology. C. elegans peptide GPCRs are being randomly screened with a library of peptides of the FMRFamide-related peptide (FLP) and neuropeptide-like protein (NLP) families.

Community members are invited to steer the project’s progression. You can help us prioritize peptide and GPCR candidates by contacting us.