This project intends to prepare the commercialization of a new, patent-protected, generic technology to identify and characterize potential drugs acting at G-protein-coupled receptors (GPCRs). GPCRs represent prime targets for therapeutic drugs, variously estimated at 25-50% of all therapeutic targets, including multi-billion € drugs for major diseases, such as beta-blockers or antihistamines. However, of the hundreds of GPCRs, only 82 are currently used as therapeutic targets, and many still lack the identification of their endogenous ligands, indicating the vast potential of these receptors for further drug development.The project is based on results of the ERC-AdG “TOPAS” (ID: 232944), where we have developed sensors for receptor activation and signaling based on fluorescence resonance energy transfer (FRET). In particular, we have developed new sensors that contain a GPCR and two fluorophores, capable of directly reporting receptor activation. The University of Würzburg has obtained broad patent rights for such sensors.Such FRET-based receptor screening assays (FRESCA) have the potential to discover new, innovative GPCR drugs. We intend to explore the usability and scalability of FRESCA for drug screening purposes in the pharmaceutical and biotech industry. We will validate FRESCA in comparison to current standards, and under high-throughput screening conditions. We expect that FRESCA can replace standard radioligand binding assays as the first line of drug screening. FRESCA further show the potential to define the properties and effects of drug candidates at GPCRs, by measuring directly the activation step (conformational change) of GPCRs rather than the many different downstream steps that are activated by GPCRs. This indicates the broad applicability of FRESCA as “all-in-one” assays for GPCRs and their commercial potential in biomedical and in drug research.We intend to establish in this project the basis for a FRESCA-based start-up biotech company.