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My research focuses on the voltage-dependent sodium and potassium channels that underlie action potentials in excitable cells, such as nerve and muscle cells. What makes these ion channels so exquisitely sensitive to membrane potential and so selective for their preferred ions? General answers to these questions are known, but glaring ignorance persists. We seek molecular, and indeed atomic, information on the detailed mechanics of these dynamic proteins, including an accounting of their internal movements and the energetics of their interactions with ions and modulatory molecules.
The techniques that I use in my research include mutations of individual amino acids of the channel protein, heterologous expression and electrophysiological assays. Our lab recently started to use the method of nonsense suppression that permits the generation of unnatural mutations within ion channels expressed in Xenopus oocytes. Although challenging, this technology allows virtually limitless possibilities for side-chain structures.
I hope that my findings will be used to enhance our understanding of the basic properties of ion channels, how they may be altered in disease states, and how diseases of excitability can be controlled.
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