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W. E. (William Esco) Moerner, the Harry S. Mosher Professor of Chemistry and Professor by courtesy of Applied Physics, has conducted research in physical chemistry, biophysics, and the optical properties of single molecules, and is actively involved in the development of 2D and 3D super-resolution imaging for cell biology. Imaging studies include protein superstructures in bacteria, structure of proteins in cells, studies of chromatin organization, and dynamics of regulatory proteins in the primary cilium. Using powerful microscopes optimized for tracking of single objects in cells, the motions of proteins, DNA, and RNA are being measured in three dimensions in real time to understand processing and binding interactions. A related research area concerns precise analysis of photodynamics of single trapped biomolecules in solution, with applications to photosynthesis, protein-protein interactions, and transport measurements.Born on June 24, 1953 at Parks Air Force Base in Pleasanton, California, Professor Moerner was raised in San Antonio, Texas. He attended Washington University as a Langsdorf Engineering Fellow, graduating in 1975 with degrees in Physics and Electrical Engineering (both B.S. with top honors), and Mathematics (A.B. summa cum laude). His doctoral research in physics at Cornell University (M.S. 1978, Ph.D. 1982) employed tunable infrared lasers to explore infrared vibrational modes of impurities in crystals. In 1982, he moved from New York to San Jose, California to join the IBM Research Division developing spectral holeburning for frequency domain optical storage and photorefractivity for dynamic hologram formation. After 13 years at IBM, Dr. Moerner accepted a position as Distinguished Professor of Physical Chemistry at UC San Diego, where he broadened his research to include biological systems and biophysics. Recruited to the Stanford Chemistry Department faculty in 1997, he served as Chair of the department from 2011 to 2014.Professor Moerner’s scientific contributions were recognized with the 2014 Nobel Prize in Chemistry "for the development of super-resolved fluorescence microscopy." One method to surpass the optical diffraction limit (PALM/STORM) uses single-molecule imaging combined with a control mechanism to keep the concentration of emitting molecules at a very low level, followed by sequential localization to reconstruct the underlying structure. The fundamentals of this idea came from early work in the Moerner lab: optical detection and imaging of single molecules (1989) combined with blinking and switching at low temperature, as well as the discovery of optical control of single copies of green fluorescent protein at room temperature (1997). Among many other honors and awards, Professor Moerner was elected fellow of the American Physical Society, Optical Society of America, American Association for the Advancement of Science, American Academy of Arts and Sciences; and member of the National Academy of Sciences.Today, the Moerner Laboratory uses laser spectroscopy and microscopy of single molecules to probe biological processes, one molecule at a time. Primary thrusts include development and application of fluorescence microscopy far beyond the optical diffraction limit by PALM/STORM and STED approaches, single-molecule tracking in complex cellular environments, invention and validation of methods for precise and accurate 3D optical microscopy in cells, and trapping of single photosynthetic biomolecules in solution for extended study. Through a variety of collaborations, these approaches are applied to explore protein and oligonucleotide localization patterns in bacteria, measure structures of amyloid aggregates in cells, define the behavior of signaling proteins in the primary cilium, quantify photodynamics for photosynthetic proteins and enzymes, and observe the dynamics of DNA and RNA in cells and viruses.Please visit the Moerner Lab home page for more information.
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Most biophysical or chemical experiments in condensed matter measure the average behavior of a huge number, N, of molecules, where N may range from millions to billions to Avogadro's Number. At the same time, most theoretical models are intended to describe the behavior of a single molecule interacting with its surroundings, and averaging over the number of molecules N is normally required to compute an observable. Using precision laser spectroscopic techniques, we have been detecting and probing the detailed properties of individual impurity molecules hidden deep inside a cell, in a protein, or even in a liquid, i.e., the ultimate limit of N=1. This was first done in the Moerner Lab in 1989, and has since expanded dramatically to include many groups around the world. A key reason for doing this is to explore heterogeneity that is normally obscured by ensemble averaging. Studying one individual molecule in a solid means we are working with an extremely small number of moles of material. You might be aware that the international standards organization, IUPAC, has defined several new prefixes: zepto- for 1E-21, and yocto- for 1E-24. Thus 1 molecule is equivalent to 1.66 yoctomoles. But we think this is unwieldy. Thus we define a new prefix guaca- so that (with apologies to Prof. Avogadro) 1 guacamole = 1 / ( Avocado's Number) of moles. More seriously, it is worth recalling that each molecule we are probing is only 1 or 2 nanometers in size. This means that when we use a laser to select one probe molecule, we can sense details of the immediate local environment of a truly nanoscopic probe. To achieve this extreme reduction of the concentration and reach the single-molecule level, we use either (a) extremely low concentrations and diffraction-limited confocal, TIRF, or far-field microscopy, or (b) near field optical excitation to pump sample volumes much smaller than the diffraction limit, or (c) superresolution imaging by single-molecule active control. By studying a large number of individual molecules one at a time, we are able not only to observe how the usual ensemble average behavior is formed, but also to see unexpected, surprising behavior normally hidden by the usual ensemble averaging. The phenomena under study include protein localization patternd in bacteria, chaperonin proteins, and new fluorophores for active-control superresolution imaging. By dispersing the emitted light, even the vibrational mode spectrum of a single molecule may be measured! By measuring correlations in the emitted photon stream, fast dynamics including environmental fluctuations, or the purely quantum-mechanical behavior termed photon antibunching may be probed. In biomolecules, we observe fascinating differences in behavior due to conformational states, local environments, or enzymatic cycle, all of which are obscured in large N experiments.Importantly, a single molecule can be viewed as a probe of its immediate local nanoenvironment on the scale on the order of the molecular size (~1 nm). Because single molecules are nanoscale emitters, when active control is used to turn molecules on and off, it is possible to build up a super-resolution image of the sample, far beyond the optical diffraction limit, typically on the 40 nm scale. Several advanced optical techniques for obtaining thee-dimensional information from single-molecule photoswitching are underdevelopment, and we apply these methods to imaging a variety of cellular structures in bacteria and in mammalian cells and to tracking of RNA in living yeast.