The structural functions and drug discovery of GPCRs G protein-coupled receptors (GPCRs) are the most popular drug targets. It has been estimated that about 40% of the marketed drugs are targeting GPCRs. We combine the traditional biochemistry and structural biology with the up-to-date computational biology to elucidate the activation process for GPCRs at plasma membrane environment. We have also made tremendous progress in GPCR drug discovery. This is represented by a series of published works, including Chemical Science 2018 (doi:10.1039/C8SC01680A), Trends in Pharmacological Sciences 2017 (doi:10.1016/j.tips.2017.08.004), Angew Chem 2016 (doi:10.1002/anie.201603766), Angew Chem 2015 (doi:10.1002/anie.201501742), Nature Communications 2014 (doi:10.1038/ncomms5733) and many others.
The structures and signalling of ion channels We recently published the first high-resolution structure of a mammalian pentameric ligand gated ion channel, the serotonin 5-HT3 receptor, by X-ray crystallography of detergent purified receptor (Nature 2014, doi:10.1038/nature13552.). We will continue this research using cryo-electron microscopy to elucidate in atomic detail by time-resolved structural analysis the entire process of receptor activation from a closed to an open channel in native plasma membrane fragments, i.e. without any receptor purification/reconstitution process. We have also illuminated the activation process of 5-HT3 receptor sucessfully using all-atom long time scale molecular dynamics simulations (Structure 2016, doi:10.1016/j.str.2016.03.019).
Developing new biotechnology for membrane protein signalling dections Based on our pioneering developments of labelling proteins in live cells with fluorescent probes, we continue research resolving the interaction network of membrane proteins with cellular signalling proteins in living cells fluorescence microscopy with single-molecule resolution. We are establishing and extending our current curricula in cellular biophysics