Introduction
Conformational biosensors report the structural rearrangements of a GPCR as they happen in living cells, upstream of any signaling readout. This Masterclass covers the principles of FRET, BRET, and single-color conformational biosensors, from the development of resonance energy transfer methods to fluorophore selection, sensor architecture, and optimization for sensitivity and specificity. It then compares site-specific fluorescence labeling strategies, their common pitfalls, and how to evaluate labeling efficiency.
Coverage extends to the fluorescence spectroscopy and microscopy methods that read these sensors, published case studies on receptor activation and signaling, and applications in mechanism-of-action studies, ligand profiling, target validation, and high-throughput screening. Intended for scientists with a working knowledge of GPCR pharmacology who use, or plan to build, cell-based activation assays.
Instructors
Katarina Nemec
Katarina Nemec works at the intersection of GPCR molecular pharmacology, biosensor design, high-throughput screening, and data-driven drug discovery. She recently joined the High Throughput Biology team at Boehringer Ingelheim, where she supports the advancement of pipeline candidates.
Trained as a pharmacist, she earned her doctorate in Biomedicine in Martin Lohse's laboratory, where she designed conformational biosensors to study GPCR activation and signaling dynamics and showed how RAMP proteins modulate PTH1R pharmacology. As a Scientist in Madan Babu's lab at St. Jude Children's Research Hospital, she developed multiplexed screening approaches and studied the developmental expression dynamics of GPCRs.
In this Masterclass she brings biosensor design and its translation to screening and drug discovery.
Romy Thomas
Romy Thomas studies how GPCRs activate, how they select their G proteins, and how ligands shape signaling, combining live-cell approaches with in vitro biochemical methods. She is a postdoctoral researcher in Brian Kobilka's lab at Stanford University.
She engineers GPCR biosensors and uses fluorescence spectroscopy to follow receptor dynamics and signaling in intact cells. She is first author of a 2026 Nature study that used genetic code expansion and bioorthogonal labeling to build a panel of single-color biosensors for the M2 muscarinic receptor.
In this Masterclass she brings site-specific labeling and the spectroscopy methods that read GPCR activation in living cells.