David C. Gadsby, Ph.D.
Patrick A. Gerschel Family Professor Emeritus
Cell membranes contain millions of embedded proteins that control ion movements into and out of the cell. This ion flow underlies such vital functions as electrical signaling in nerve, heart, and muscle cells; cell volume regulation; secretion of hormones and neurotransmitters; fertilization; and kidney function.
Two principal classes of proteins regulate ion movement across membranes: pumps and channels. Channels allow ions to flow rapidly down their electrochemical gradients, while pumps move ions relatively slowly, thermodynamically uphill, thereby building up those gradients.
Gadsby has used position-specific mutagenesis, combined with structural modeling and biochemical and electrical measurements, to examine the mechanisms of two biomedically important ion transport proteins. One, the Na+/K+-adenosine triphosphatase, is a pump crucial to animal cell life, and the other, CFTR (cystic fibrosis transmembrane conductance regulator), is a Cl⁻ ion channel. Mutations in the CFTR gene are responsible for cystic fibrosis. Mutations in the Na+/K+ pumps of brain neurons have been found responsible for childhood neurological disorders.
Gadsby’s work has suggested that, whereas an ion channel can be viewed as a transmembrane ion pathway controlled by a gate at one end, an ion pump can be viewed as a modified ion channel governed by gates at both ends. A pump’s gates must be tightly coupled so that both are never open simultaneously. In both the Na+/K+ pump and CFTR Cl⁻ channel, these conformational changes are driven by binding and hydrolysis of adenosine triphosphate (ATP).
Gadsby’s lab has found that during the normal Na+/K+ transport cycle, a certain conformation of the Na+/K+ pump can be hijacked by extracellular protons to access the cell interior. The probability of proton entry through any given Na+/K+ pump depends on the extracellular proton concentration. The Na+/K+ pump is thus a hybrid transporter, a protein with two distinct functions.
Gadsby received his Bachelor’s and Master’s degrees from Trinity College at the University of Cambridge, and his Ph.D. in physiology from University College London. He joined Rockefeller as an assistant professor in 1978. He is a member of The Royal Society.