We mostly study two molecular machines: the sodium/potassium pump (Na⁺, K⁺-ATPase), which transports hundreds of Na and K ions across the cell membrane every second, and the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channel, whose open conformation allows millions of chloride ions to cross the membrane each second. Both are ATPases and harness the free energy of ATP binding and hydrolysis to generate the conformational changes that control ion transport. We use mutagenesis, and biochemical and high-resolution electrical methods to examine those conformation changes, sometimes in one molecule at time.