FUNCTIONALIZATION OF ORPHAN G-PROTEIN COUPLED RECEPTORS

All cells sense their environment through receptors that are located at the cell surface and act as antennas for signaling molecules. G-protein coupled receptors (GPCRs) form the largest receptor family in the human genome. These receptors are essential to virtually every physiological process and represent targets of half of the available prescription drugs. Despite vast, long-standing efforts, many GPCRs, the so-called orphans, remain enigmatic because neither their environmental stimuli nor their physiological responses are understood. The central hypothesis of our research project is that functionalized orphan- GPCRs, in which activation by the unknown ligand is replaced with that of a known stimulus, will enable their activation and study in living cells. This approach will allow us to for the first time describe the molecular and cellular function of orphans and open new avenues towards the understanding and manipulation of receptors in health and disease.