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, 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.