Biographical Sketch

Professor and Jules Stein Professor of Ophthalmology; PhD, Chemistry, Stanford University; AFOSR-NRC Postdoctoral Fellow, Chemistry, Stanford University.

Description of Research

Phototransduction, voltage-dependent membrane switching and active membrane transport are our primary research focuses. These processes involve membrane proteins that function through conformational changes regulated by light, transmembrane potential and energy sources, respectively. The immediate goal is to determine the molecular mechanisms underlying these conformational transitions.

Studies in the above systems all require methods capable of providing static and time-dependent structural information in membrane-bound proteins. An extremely promising approach is the nitroxide "spin-labeling" method of electron paramagnetic resonance (EPR) spectroscopy. In collaboration with molecular biology laboratories, we are currently employing site-directed mutagenesis to provide specific sites for attachment of spin labels in membrane proteins. With a sufficient number of such labeled mutants, global structural and dynamical information of a highly detailed nature is obtainable through studies of the EPR spectra. Recent advances in EPR spectroscopy (loop-gap resonator technology) have made it possible to carry out elegant double resonance (ELDOR) and time domain (saturation recovery) EPR experiments on the labeled proteins. These approaches are now providing an entirely new dimension of information regarding protein structure and function.

Key Words

Biochemistry: membrane proteins; site-directed spin labeling; EPR spectroscopy.