In order to transduce a signal of a hormone or prescription drug across the plasma membrane G-protein-coupled receptors (GPCRs) need to undergo conformational changes. The focus of our research is to investigate such conformational changes during GPCR activation and deactivation. Therefore we develop FRET-based probes for GPCRs to image the conformational change in living cells and millisecond time resolution. The use of such FRET-based sensors allows us to study receptor ligand interaction directly at the level of the receptor itself. Thus we are able monitor the effects of potential future drugs at the protein level and can correlate the observed data with effects on different signalling pathways triggered by receptor activation.

Receptor interaction with b-arrestin is an important regulatory key element in the termination of G-protein-dependent receptor signalling. The interaction of a GPCR and b-arrestin is regulated by ligand binding and receptor phosphorylation by specific receptor kinases. Since β-arrestins not only turn off G-protein-dependent-signalling but represent starting points for novel signalling cascades, we are also interested to investigate receptor ligands which are able to discriminate between G-protein and b-arrestin mediated receptor signalling. Such compounds are called biased ligands and are of great value for basic research and hold the promise for fewer side effects for patient treatment.

During the Summer School, we focus on real-time analysis of receptor activation in living cells using FRET based bio-sensors for the signal transduction pathways involved in receptor signalling. Applied techniques will include heterologous expression in mammalian cells, plate-reader assays and microscopy of signal transduction in living cells.