Pentameric ion channels as targets for drug discovery in human disease

In this research project, I will focus on identifying the structure a subfamily of transient receptor potential channels, TRPM3, and relating its function to such. This is an attractive member because of its involvement in thermosensation and many somatosensory and metabolic diseases and cancers. To accomplish this, the protein of interest needs to be cloned, extracted from the membrane, and applied to large-scale purifications to obtain milligram amounts of protein. To resolve structure and function, simultaneous crystallization screens and cryo-electron microscopy (EM) experiments need to be carried out to determine optimal buffer conditions and suitable constructs for successful crystal growth or EM imaging. Finally, diffraction data from suitable crystals or EM particle reconstruction will be used for model building, refinement, and structure-function validation using electrophysiology.