Top 1 Biorxiv Papers Today in Pharmacology And Toxicology


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#1. DCyFIR: a high-throughput CRISPR platform for multiplexed G protein-coupled receptor profiling and ligand discovery
Nicholas J Kapolka, Geoffrey J Taghon, Jacob B Rowe, William M Morgan, Jay F Enten, Daniel G Isom
More than 800 G protein-coupled receptors (GPCRs) comprise the largest class of membrane receptors in humans. While there is ample biological understanding and many approved drugs for prototypic GPCRs, most GPCRs still lack well-defined biological ligands and drugs. Here, we report our efforts to tap the potential of understudied GPCRs by developing yeast-based technologies for high-throughput CRISPR engineering and GPCR ligand discovery. We refer to these technologies collectively as Dynamic Cyan induction by Functional Integrated Receptors: DCyFIR. A major advantage of DCyFIR is that GPCRs and other assay components are CRISPR-integrated directly into the yeast genome, making it possible to decode ligand specificity by profiling mixtures of GPCR-barcoded yeast strains in a single tube. To demonstrate the capabilities of DCyFIR, we engineered a yeast strain library of 30 human GPCRs and their 300 possible GPCR-Gα coupling combinations. Profiling of these 300 strains, using parallel (DCyFIRscreen) and multiplex (DCyFIRplex) DCyFIR...
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biorxivpreprint: DCyFIR: a high-throughput CRISPR platform for multiplexed G protein-coupled receptor profiling and ligand discovery https://t.co/dBTUWeF52w #bioRxiv
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