Professor, Department of Pediatrics, Institute of Molecular Pediatric Sciences, Committee on Molecular Medicine/MPMM, Biochemistry & Molecular Biophysics
Ph.D., UCLA, 1990
The University of Chicago
929 East 57th Street
Chicago, IL 60637
Phone: (773) 834-4747
Structure-Function and Energy Transduction Mechanisms in Ion Channels Using Functional Spectroscopic and Structural Approaches
Most membrane proteins have moving parts that help execute their specific function, often in response to an external stimulus. Our research aims to understand the molecular mechanisms underlying the transduction of different forms of energy into protein motion; in particular the different molecular mechanisms of ion channel gating. We are equally interested in protein structure as in protein dynamics, for it is the dynamic behavior of a molecule what links structure to function.
Therefore, we rely on spectroscopic methods, and in particular reporter group techniques (EPR, Fluorescence), to study channels and other membrane proteins embedded in a fluid lipid bilayer. Static structural analyses are pursued by X-ray crystallography. These structural techniques are all interpreted in the context of high-resolution functional methods (single channel, macroscopic and gating current electro-physiological measurements). Using these strategies, we aim to answer the following long-term questions:
1- What is the structural pathway followed in the transition from the closed to the open conformation in K+ channels, and what is the nature of this conformational wave?
2- What is the influence of the selectivity filter on channel gating?
3- What is the native structure of voltage-dependent channels and how is transmembrane voltage sensed?
4- How do voltage sensor and gate couple to open the channel?
5- What is the molecular basis of mechanosensitivity in prokaryotic channels? How do membrane bilayer deformations are transduced into large protein rearrangements leading to channel opening?