Research in the Chanda Lab focuses on structural mechanisms that underlie gating of members of the voltage-dependent ion channel family. Our overarching goal is to understand the interrelationships between structure, function and dynamics in order to develop an integrated view of how ion channels work. If we are successful in this endeavor, we will be able to engineer new ion channels that exhibit exotic behavior or create small molecules that may selectively repair defective ion channels. Defects in ion channels underlie diseases such as cardiac arrhythmias, generalized epilepsies, cystic fibrosis and polycystic kidney disease to name a few. Our approach combines cutting edge electrophysiological methods such as voltage-clamp fluorimetry and single channel recordings with high‑resolution structural analysis such as x-ray crystallography. More recently, we have invested considerable effort to develop new single molecule fluorescence methods to study ligand dependent modulation of voltage-gated ion channels. Our research is constantly evolving but very broadly our research effort is directed towards these central questions. 1. How do ion channels sense temperature? What are molecular and structural determinants of temperature-sensing? 2. What are the mechanisms of voltage-gating? Despite overall conserved structure, why do some channels open when the membrane is hyperpolarized whereas others open upon depolarization? 3. What are the mechanisms of ligand-dependent activation in voltage-gated ion channels? How does a structurally symmetric ion channel exhibit both positive and negative cooperativity?