Picoquant Young Investigator Award:
Visualizing and Manipulating Cell Surface Proteins
Selective targeting of biomolecules for labeling, visualization and functional manipulation is at the forefront of Chemical Biology. We employ approaches from photopharmacology and fluorophore design to enable biomolecule labeling and control, while bringing dye properties to the next level. As such, azobenzene photoswitches enable reversible ON and OFF remote control of metabotropic glutamate receptor 2 (mGluR2), a class C G Protein Coupled Receptor (GPCR) involved in neurotransmission with light. This optical regulation of membrane excitability has led to the latest generation of photoswitches to probe working memory with light in vivo. More generally, the precise labeling of GPCRs in defined cellular compartments is important to differentiate functional receptor pools. For this reason, we extend labeling techniques with new properties to separate and interrogate different cellular protein pools, such as the membrane bound and the intracellular populations. We successfully highlight this by advanced SNAP-tag substrates to determine different GPCR stoichiometries in various cellular compartments. Expanding on this, we recently targeted endogenous GPCRs with custom- tailored fluorescent antagonists. In order to pave the way for better image quality, we think in and pursue unconventional ways in the design and synthesis of fluorophores for super- resolution imaging in live cells. In our latest efforts, we endow fluorophores with deuterium to yield dyes with increased fluorescent lifetimes, higher photostability and augmented brightness, thereby opening new applications in nanoscopy and single molecule tracking.
We thank for the kind support by: