Faculty of Molecular and Cellular Physiology
Axel Brunger (Department Chair)
Jointly appointed in Neurology & Neurological Sciences, Photon Science and, by courtesy, Structural Biology
We investigate the molecular mechanisms of synaptic neurotransmitter release by conducting single-molecule/particle reconstitution and imaging experiments, combined with high-resolution structural studies (by X-ray crystallography and electron cryo-microscopy) of the synaptic vesible fusion machinery. Other interests include the development of advanced methods for biomolecular structure determination.
Jointly appointed in Physics
From January 2009 until April, 2013, Dr. Chu served as the 12th U.S. Secretary of Energy during President Obama's administration. Prior to his Cabinet post, he was the Director of Lawrence Berkeley National Lab, Professor of Physics and Professor of Molecular and Cell Biology, University of California Berkeley and Professor of Physics and Applied Physics at Stanford University. Previous to those posts, he was with AT&T Bell Laboratories. Dr. Chu is the co-recipient of the Nobel Prize for Physics (1997) for his contributions to the laser cooling and trapping of atoms. His other areas of research include tests of fundamental theories in physics, atom interferometry, study of polymers and biological systems at the single molecule level, and biomedical research. While at Stanford, he helped start Bio-X, a multi-disciplinary initiative that brings together the physical and biological sciences with engineering and medicine. More recently, he has focused on how to transition to a sustainable future.
We are interested in the structure, dynamics and function of eukaryotic transport proteins mediating ions and major nutrients crossing the membrane, the kinetics and regulation of transport processes, the catalytic mechanism of membrane embedded enzymes and the development of small molecule modulators based on the structure and function of membrane proteins.
Jointly appointed in Structural Biology
Structural and functional studies of transmembrane receptor interactions with their ligands in systems relevant to human health and disease - primarily in immunity, infection, and neurobiology. We study these problems using protein engineering, structural, biochemical, and combinatorial biology approaches.
Touch is the first sense to develop, the last to fade, vital to daily living and poorly understood. We investigate the biophysics and mechanics of touch sensation by combining in vivo electrophysiology with genetics and novel tools for mechanical stimulation, through quantitative behavioral studies, light and electron microscopy. Other interests include developing simple animal models of peripheral sensory neuropathy and investigating how neurons resist mechanical stress.
Jointly appointed, by courtesy, in Chemical and Systems Biology
The Kobilka lab investigates the molecular mechanisms of G protein coupled receptor signaling. G protein coupled receptors are responsible for the majority of cellular responses to hormones and neurotransmitters, as well as the senses of sight, olfaction and taste. We use a variety of biochemical and biophysical approaches to characterize the structure and dynamic properties of these receptors that are responsible for their versatile signaling behavior.
Calcium signaling mechanisms in lymphocytes. Generation of calcium signals by channels, pumps and organelles, and the effects of calcium dynamics on the specificity of T-cell gene expression. In vivo calcium imaging with two-photon microscopy. Patch-clamp studies of the biophysics and regulation of store-operated calcium channels.
Daniel Madison (Director of Graduate Studies)
Mechanisms of synaptic transmission and plasticity in mammalian hippocampus using electrophysiological techniques. Study of long-term potentiation and mechanisms underlying memory formation in the central nervous system.
We are interested in the molecular mechanisms of ion channels and transporters. We study these mechanisms using a combination of biophysical methods to probe protein structure and dynamics together with electrophysiological analysis to directly measure function.
Research in the lab is focused on decoding the molecular basis of transmembrane signaling and transport. The particular systems we study lie at the intersection of human health and protein science. We utilize a broad range of methods in structural biology, protein biophysics, pharmacology, and protein engineering to understand how cells recognize and respond to their extracellular environment and maintain intracellular homeostasis.
We study the primary cilium, a once-obscure cellular organelle recently "re-discovered" for its role in a number of signaling pathways. Defects in cilium biogenesis lead to a variety of hereditary disorders characterized by retinal degeneration, kidney cysts and obesity. Our goal is to characterize these disorders at the molecular and cellular levels to gain insight into the basic mechanisms of primary cilium biogenesis and to discover novel ciliary signaling pathways.
Stem cell dynamics during functional adaptation of the Drosophila midgut. Physiological signals and cellular interactions that distinguish stem-based organ remodeling from organ renewal. Impact of tissue architecture on stem cell behavior. Genetic perturbation of stem cell regulation, fixed and live tissue imaging, and quantitative morphometric analysis.
Georgios Skiniotis, a recently arrived professor in the department, is a structural biologist with expertise in electron cryo-microscopy (cryoEM). Skiniotis has exploited the power of cryoEM to study a wide range of important biological “machines” or macromolecular assemblies. His main interests are on the mechanisms of transmembrane signal instigation with a particular focus on G protein-coupled receptors and cytokine receptors. The application of cryoEM to such systems has also driven him to explore and refine approaches for resolving technically challenging problems.
Thomas C. Südhof
Jointly appointed, by courtesy, in Neurology & Neurological Sciences and Psychiatry & Behavioral Sciences
In brain, neurons primarily communicate with each other at synapses, which are highly plastic, and not only transfer, but also process and store information. My laboratory is interested in how synapses are formed, how synapses work at a molecular level and change during synaptic plasticity, and how synapses become dysfunctional in diseases such as autism and other neuropsychiatric disorders. To address these questions, my laboratory employs a variety of approaches ranging from biophysical and biochemical studies to electrophysiological and behavioral analyses of mutant mice.
Jointly appointed in Structural Biology and Photon Science
Molecular interactions that underlie the establishment and maintenance of cell and tissue structure are studied with a variety of biochemical, structural, and biophysical methods. Specific areas of interest include cadherin-based adhesion and its interaction with the cytoskeleton, the relationship between cell-cell junction formation and generation of cell polarity, and the Wnt signaling pathway that controls cell fate determination.
Department of Anesthesiology
Our laboratory investigates the cellular and molecular mechanisms of pain and its control by opioids. When chronic, pain is no longer an essential warning system critical to our survival, but a disease that severely affects the quality of life of many patients. We search to identity the neurons that participate in generating the sensation of pain and to uncover the molecular mechanisms that regulate neural activity in pain circuits. One of our goals is to elucidate the mechanisms by which opioids such as morphine generate analgesia and detrimental side effects, including addiction, to develop more efficient and safer analgesics. To this end we combine a variety of experimental approaches including molecular and cellular biology, neuroanatomy, electrophysiology, optogenetics and behavior.
Our laboratory explores the development, structure, function and disorders of the brain’s neural circuitry. The lab’s experimental approach has typically begun with the invention of a new optical imaging method followed by applications of that method to attack important but previously untractable experimental challenges. Most recently, the lab invented a unique high-resolution proteomic imaging method called “array tomography”, and are now working to apply this novel method to explore the molecular architecture of cortical microcircuits in mouse and human. This work is currently focused on efforts to identify the circuit loci of the specific changes in synaptic connectivity associated with specific memory traces, i.e. the physical “engrams” of experience.
Richard Aldrich- 1990 to 2005
Now at The University of Texas, Austin
Richard Scheller- 1990-2001
Now at Genentech
Thomas Schwarz- 1990-2000
Now at Children's Hospital Boston