MD, University of Geneva, Switzerland

Molecular Pharmacology and Biological Chemistry
Integrated Graduate Program

Office Phone: 312.503.3375
Lab Phone: 312.503.3381

Email

Research

My lab studies the structure and function of ion channels, a family of membrane proteins that play many key roles in neuroscience and which are a major target of essential drugs used in clinical medicine. About half of all genes in a typical genome code for membrane proteins, yet we know very little about their structure and function. Because ion movement across membranes can be measured with exquisite sensitivity, ion channels have always been at the vanguard of functional studies of membrane proteins, and as a consequence we have learned a great deal about how they function. Until recently, however, ion channels, like so many other membrane proteins, had proven very difficult to study at the structural level. The recent high-resolution description of two unrelated ion channels has opened up the field of structure-function in ion channels, and we are now in a position to ask detailed questions about how function is achieved through structure in this essential class of proteins.

How do voltage-dependent ion channels sense the membrane potential? Through what structural rearrangements do these channels achieve voltage-dependent ion flow across the membrane? How can highly dynamic proteins maintain such outstanding control of what sorts of ions are allowed to pass? These are some of the questions that we attempt to answer.

The lab uses both structural and functional approaches to address these questions. The main structural technique that we employ is site-directed spin labeling and EPR spectroscopy, an emerging and powerful structural technique that is not limited to static structure, but instead is also capable of resolving dynamic structural changes that occur during function. Given the highly dynamic nature of membrane proteins, it is essential that the structural technique used to study them be capable of resolving dynamic structural changes. Our main functional approach is electrophysiology. With electrophysiology, ion channels can be studied in real time as they undergo the structural rearrangements necessary for function. By combining these two powerful and yet complimentary techniques we are taking a two-pronged approach to the long-term goal of achieving a mechanistic understanding of ion channel function.

Publications

Lenaeus MJ, Vamvouka M, Focia PJ, Gross A. (2005) Structural basis of TEA blockade in a model potassium channel. Nat Struct Mol Biol. 12:454-459.

Brent Kelly and Adrian Gross (2003). Potassium channel gating observed with site-directed mass tagging. Nature Structural Biology 10: 280-284.

Adrian Gross and Wayne Hubbell (2002). Identification of protein side chains near the membrane-aqueous interface: a site-directed spin labeling study of KcsA. Biochemistry 41: 1123-1128.

Johannes le Coutre, Julian P. Whitelegge, Adrian Gross, Eric Turk, Ernest M. Wright, Kym Faull, and H. Ronald Kaback (2000). Proteomics on full length membrane proteins using mass spectrometry. Biochemistry 39: 4237-4242.

Adrian Gross, Linda Columbus, Kalman Hideg, Christian Altenbach, and Wayne Hubbell (1999). Structure of the KcsA potassium channel from Streptomyces lividans: A site-directed spin labeling study of the second transmembrane segment. Biochemistry 38: 10324-10335.

Wayne Hubbell, Adrian Gross, Ralf Langen, and Michael Lietzow (1998). Recent advances in site-directed spin labeling of proteins. Current Opinion in Structural Biology 8: 649-656.

Adrian Gross and Roderick MacKinnon (1995). Agitoxin footprinting the Shaker potassium channel pore. Neuron 16: 399-406.

Adrian Gross, Tatiana Abramson, and Roderick MacKinnon (1994). Transfer of the toxin receptor to an insensitive potassium channel. Neuron 13: 961-966.

Curricula

Pharmacology and Toxicology
Structural Biology and Biochemistry

Links

Publications by Adrian Gross