The Minor Lab merges structural, biochemical, genetic, and electrophysiological methods to dissect the mechanisms of action of ion channels, the complex protein machines that generate electrical signals in the heart, brain, and sensory systems.

Ion channels are principal conduits for information transfer into and out of cells. We are particularly interested in how ion channels function as macromolecular signaling complexes, how these complexes generate and integrate signals, and how they misfunction in human disease. We use a range of biochemical and biophysical tools to examine the molecular structures and detailed energetics that are integral to ion channel function. Our research relies heavily on X-ray crystallography, small angle X ray scattering (SAXS), isothermal titration calorimetry, circular dichroism, and analytical ultracentrifugation. Because protein structure is intimately tied to function, an equally critical part of our research implements structure based tests of the mechanisms of ion channel action and regulation in live cells using electrophysiology.

A second interest of the lab is in the development of methods to identify molecules that modify ion channel function. We are developing a variety of genetic selections to identify novel ion channel blockers and activators and uncover how they act. This research addresses a particularly pressing need as many types of ion channels lack any robust pharmacology, a situation that severely limits the ability to connect ion channel genes with their physiological functions. The development of new selective inhibitors and activators of channel function should provide new tools for ion channel research and may lead to the development of novel, ion channel directed pharmaceuticals.

Finally, as a member of both the Membrane Protein Expression Center (MPEC) and Center for Membrane Protein Structure (CSMP) our lab has a committed effort towards developing methods for the overexpression of eukaryotic membrane proteins with the goal of determining high-resolution structures. Our efforts aim at understanding the workings of ion channels and transporters that power the cell through their involvement in mitochondrial function.