Project R-11946

Investigation of G-protein coupled receptors conformational dynamics via single-molecule fluorescence microscopy. (Research)

G-protein coupled receptors (GPCRs) orchestrate critica! processes in the human body, including neurotransmission, neurodegeneration, vision, inflammation, pain, etc. In this project, the pipeline for systematic studies of GPCR conformational dynamics based on advanced methods of single-molecule fluorescence microscopy wil! be developed and applied to one of the most well-described GPCR - A2A-adenosine receptor. This receptor is considered as a prospective target for drugs against insomnia, chronic pain, depression, and Parkinson's disease. The first steps of the project will focus on instrumental challenges. During this phase, we wil! use the known protein reé:overin as a model protein avoiding known membrane protein challenges. The scheduled experiments wil! for the first time provide data on conformational dynamics of recoverin with single­ molecule resolution. Further studies of conformational dynamics of calcium sensors wil! open the gates for clinical applications in the treatment of a wide spectrum of neurological and neurodegenerative diseases from autism to Parkinson's disease and Alzheimer's disease.

01 September 2021 - 31 December 2023