Dr. John L. Spudich
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Biochemistry and Molecular Biology
Center for Membrane Biology
Department of Microbiology and Molecular Genetics
My primary interest is the mechanism by which photosensory receptors sense and transmit information concerning the color, intensity, and pattern of light in the environment. Our laboratory studies a widespread class of photoactive receptor proteins (rhodopsins) that consist of seven transmembrane helices connected by interhelical loops. The helices form a pocket for the photosensitive molecule vitamin-A aldehyde (retinal), and the receptor proteins physically couple to protein transducers that relay signals to sensory pathways in the cytoplasm. These photosensitive seven helix proteins are used for visual processes of various degrees of sophistication, ranging from detection of light for motility responses (phototaxis) by single-cell microorganisms to high-resolution color image detection by animal eyes.
Recently microbial rhodopsins have proven useful for modulating membrane potentials in cells, especially in the photocontrol of neuron firing. Such use has defined a new technology called "optogenetics". Algal phototaxis receptors (called channelrhodopsins) are light-gated channels that depolarize cell membranes and therefore can be used to activate neurons, whereas light-driven ion pumping rhodopsins from Archaea hyperpolarize the cell membrane and silence neurons. In addition to studying the molecular mechanisms of these photoactive proteins, we also are interested in further developing microbial rhodopsins to expand the optogenetic toolbox.
Our research is multidisciplinary, including molecular genetic techniques (cloning, site-specific and random mutagenesis), protein biochemistry (purification, membrane reconstitution, crystallization), biophysics (laser flash spectroscopy, electrophysiology), and cell biology (computerized cell motion analysis, fluorescence microscopy). Tutorial projects typically focus on one or two of these approaches.