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βIt is very easy to answer many fundamental biological questions; you just look at the thing!β
β Richard Feynman (1965 Nobel Prize in Physics)
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Lipid membranes allowed cellular life to emerge on Earth by enabling compartmentalization but how does the exchange of matter and information across this essential barrier occur? We make it our mission to answer this question by elucidating the mechanism of membrane proteins that carry out this fundamental process. Ion channels, transporters and receptors are our primary focus. Topics surrounding signal transduction, substrate selectivity, gating, regulation and dynamics hold a particular fascination among us. We often develop models of how these molecular devices operate by simply looking at them. Single-particle analysis (SPA) by electron cryo-electron microscopy (cryo-EM) is one of our main tools we use to visualize membrane proteins and their assemblies at the atomic level. We combine biophysical, biochemical, chemical biological, electrophysiological and cell biological approaches to test and refine our intuition of how these nanoscopic machines do their jobs. We are also interested in leveraging our structural and mechanistic insights to understand the genetic basis of important diseases and to find new ways of combating them.