Research Interests

Throughout my research career, I've been engaged with the mechanisms by which ion channel proteins work. These proteins, which form aqueous pores spanning the membranes of all cells, provide ionic "leak" pathways that are gated by a huge variety of biological signals - neurotransmitters, transmembrane voltage, heat, cold, Ca++, phosphorylation, membrane "stretch," G-proteins, to name a few. Channels are good inorganic chemists that exquisitely distinguish among similar "structureless" ions, allowing K+, for instance, to pass while excluding Na+, or welcoming Ca++ while rejecting Mg++. Early on, I developed a method for examining the action of single ion channel molecules in biochemically defined "artificial" membranes by high-resolution electrical recording and have exploited this technique, as well as other single-molecule methods, to infer mechanisms of channel gating and ion selection for various channel yes. Recently, I have been focusing on Cl- channels, supplementing these purely functional approaches with x-ray crystallographic analysis. These investigations have led me to follow up a recent unexpected finding - that a class of proteins long thought to be Cl- channels are in fact energy-requiring Cl- "pumps" - and accordingly I've been dragged into the unfamiliar territory of sorting out mechanisms of ion transport that are far more intricate than simple "leaks" through an aqueous pore.

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Primary Section

Section 29: Biophysics and Computational Biology

Secondary Section

Section 23: Physiology and Pharmacology