This proposal requests support for a Keystone Symposia meeting entitled G Protein-Coupled Receptors: Molecular Mechanisms and Novel Functional Insights, organized by Arthur Christopoulos and Michel Bouvier, which will be held in Alberta, Canada from February 17 - 22, 2012. The seven transmembrane-spanning G protein-coupled receptors (GPCRs) are the largest superfamily of receptors in the human genome, are involved in virtually all physiological processes, and represent the targets for at least 30% of all current medicines. Recent years have witnessed the coalescing of a number of important paradigms, including ligand- biased signalling, allosteric modulation and receptor dimerization, with substantial advances in structural determination, chemical biology and in vivo approaches to studying GPCR function. These developments will undoubtedly have a profound impact on future approaches to GPCR-based drug discovery. This meeting will focus on the interplay between these developments, and how they can be exploited to advance the translational application of cutting-edge GPCR-based research. PUBLIC HEALTH RELEVANCE: G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome, and include many potential therapeutic targets for a broad range of diseases such as neuropsychiatric and behavioral disorders, diabetes and obesity, cardiovascular disease, inflammation and cancer. The Keystone Symposia meeting on G Protein-Coupled Receptors: Molecular Mechanisms and Novel Functional Insights will provide a unique opportunity for scientists from diverse backgrounds to better understand the challenges of GPCR drug discovery from new perspectives and explore new approaches to more efficiently develop effective GPCR therapeutics.