Understanding the Spatiotemporal Aspect of GPCR Molecular Assembly and Signaling Processes in Living Cells
Xiaohan Zhou joined the Gradinaru Lab in the fall of 2020 after completing his undergraduate degree in Physics at Nanjing University. During his undergraduate study, Xiaohan was awarded the opportunity to go to Duke University as an exchange student and also served as a visiting undergraduate researcher at the Johns Hopkins University.
For his PhD project, Xiaohan aims to investigate the M1 muscarinic receptor (M1R) and A2A adenosine receptor (A2AR), two important G Protein Coupled Receptors (GPCRs) that modulate neurotransmitter release in the central nervous systems. Previous research in the Gradinaru lab focused on characterizing the quaternary structures and conformational dynamics of GPCRs and their cognate G proteins from detergent-purified samples. In contrast, Xiaohan’s work centers on imaging M1R and A2AR in live cells, with of goal of establishing their dynamic spatial distributions in the cell membrane, dissecting their engagement with G proteins in the signaling cycles, and delineating the formation and roles of oligomeric species during the process.
And as part of the CPS Research Visit Fellowship, Xiaohan proposed to learn how to stably co-express GPCRs and G proteins at single-molecule densities in vivo. During his time at Dr. Graeme Milligan’s lab in the College of Medical, Veterinary, and Life Sciences at the University of Glasgow, he explored novel fluorescence labeling strategies, such as the use of biarsenical-tetracysteine and unnatural amino acid motifs for site-specific tagging at extracellular or intracellular domains. He also gained advanced molecular and cellular biology techniques to support his PhD project examining the spatiotemporal dynamics of GPCR signaling in live cells. Due to GPCRs crucial role in cellular signaling and the central nervous system, better understanding their signaling process will allow for novel approaches in therapeutical prevention caused by its dysfunction.
