Channels and Receptors

We work on several biological targets beyond microtubules, that bring new pharmacological challenges and biological opportunities. For conceptual reasons, our research here is mostly directed towards channels (e.g. TRPs) and receptors (e.g. mGluRs).

(1) TRP channels form a family of 28 ion channels, playing prime roles in sensory integration of simultaneous signal inputs (temperature, pH, chemical ligands, etc) as well in the bulk mineral transport (homeostasis) needed for cell survival and replication. Kickstarted by the DFG Transregio SFB152 TRiPs to Homeostasis we are working on new photopharmaceutical modulators of TRP channels, for high-temporal-precision studies of their functional roles in vitro and in vivo. As high-impact sensory and signaling systems that can be exquisitely primed for chemical intervention, TRPs offer photopharmacologist fertile grounds for methodological explorations far beyond the current paradigms of "switching a blocker more-on and more-off".
Our TRP research has focused on e.g. establishing the framework of chromocontrol and ideal efficacy switching for TRPC4/5 photocontrol from cell culture to deep tissues, as a means to build in vivo photoswitchability (BioRxiv 2024; explainer); and on developing new TRP photoswitch reagents to address channels that do not yet have appropriate toolsets (e.g. BTDAzo: the first Trpc5-selective photoswitchable modulator, applied from cell culture to tissue slice in Angewandte 2022).
For an excellent introduction to sensory receptor modulation, see Colquhoun 1998.

(2) GPCRs are a monumental family of receptors in biological signaling. We have been working on chemical photoswitches to control mGluR glutamate receptors, as an excellent testbed for harnessing our unique singlet-manifold NIR-photocontrol designs, via bidirectional NIR-II E⇆Z tuning (ChemRxiv 2024) and unidirectional NIR-I Z→E actuation (ChemRxiv 2023). The aim is to bring these in vivo-suitable wavelength response methods together with our in vivo-applicable pharmacological design paradigms, to unlock non-invasive in vivo photocontrol studies in freely-moving animals.

(3) Target-based Collaborations: we collaborate to develop photoresponsive bioactive tool compounds for various cellular target systems as opportunities arise:
‣ first-in-class RORγ nuclear hormone receptor photoswitches (Angew. 2024) (Merk)
‣ first-in-class actin photo-inhibitors (optojasps: JACS 2020) later progressed into self-switch-off variants (neo-optojasps: Angew. 2022) (Trauner & Arndt)