Project R-8165

Patch-clamp fluorometry platform for unravelling the structure-function relationship of the GlyR (Research)

The glycine receptor (GlyR) is a protein involved in neuron communication. It is present in the membrane of neuron cells of the spinal cord and brain. Upon binding of glycine it transports chloride ions, thereby fine-tuning neuron activity. The alpha 3 type GlyR is a promising target to treat pain, but more fundamental insights on receptor structure and function are needed. As it comprises five subunits, different combinations of subunits lead to receptors with different properties. To investigate this, the coassembly of different GlyR subunits, and its effect on receptor structure and activity, requires new analysis methods. In this project I will investigate the GlyR using light microscopy and electrophysiology. Light microscopy allows "seeing" the receptors, i.e. their cellular distribution, composition and structure. Electrophysiology allows detecting ion flow of single channels, i.e. it allows probing their function or activity. By combining both methods on a single platform, all these readouts can be obtained for a single channel, which is crucial for linking GlyR structure with function. Finally, the different methodological developments I propose in this project are widely applicable in the life sciences, which increase the outreach of this project.

01 October 2017 - 31 March 2019