个人简介

Education: B.S., A.B., B.S., 1975, Washington University; M.S., 1978; Ph.D., 1982, Cornell University Awards: Roger I. Wilkinson National Outstanding Young Electrical Engineer, 1984; IBM Outstanding Technical Achievement Awards for photon-gated spectral hole burning, 1988, and for single-molecule detection and spectroscopy, 1992; Elected Fellow, American Physical Society, 1992; Elected Fellow, Optical Society of America, 1992; Earle K. Plyler Prize, 2001; Elected Fellow, American Academy of Arts and Sciences, 2001; Harry S. Mosher Professor, Stanford University, 2002 -; Geoffrey Frew Fellow, Australian Academy of Sciences, 2003; Fellow, American Association for the Advancement of Science, 2004; Member, National Academy of Sciences, 2007; Wolf Prize in Chemistry, 2008; Irving Langmuir Prize in Chemical Physics, 2009; Pittsburgh Spectroscopy Award, 2012; Outstanding Alumni Achievement Award, Washington University, 2013; Kirkwood Award Medal, Yale University, New Haven Section of the American Chemical Society, 2013; Peter Debye Award in Physical Chemistry, 2013; Nobel Laureate, 2014

研究领域

Biophysical/Chemical Physics/Physical

The Moerner Laboratory utilizes laser spectroscopy and microscopy of single molecules to probe biological processes, one biomolecule at a time. Primary thrusts include development and application of fluorescence microscopy far beyond the optical diffraction limit by PALM/STORM and STED approaches, invention and validation of methods for precise and accurate 3D optical microscopy in cells, and trapping of single biomolecules in solution for extended study. These approaches are applied to explore protein localization patterns in bacteria, to measure structures of amyloid aggregates in cells, to define the behavior of signaling proteins in the primary cilium, to quantify photodynamics for photosynthetic proteins and enzymes, and to observe the dynamics of DNA and RNA in cells and viruses. Research Area: Physical chemistry, chemical physics, single-molecule biophysics, super-resolution imaging, nanoparticle trapping Most physical, chemical and biophysical experiments in condensed phases measure the average behavior of a huge number of molecules, from millions to billions to Avogadro's Number. At the same time, most theoretical models describe the behavior of a single molecule interacting with its surroundings, and employ ensemble averaging over the number of molecules N to compute an observable. To explore what happens when ensemble averaging is removed, we use single-molecule optical spectroscopy and imaging, a set of ultrasensitive far-field and near-field laser techniques that allow us to detect and probe the optical properties of individual molecules (N=1). In this way we can explore truly local behavior inside a solid, a liquid, or in a biomolecular system such as a single protein or enzyme in a living cell (see Figure). Why is this new area, single-molecule optical nanoscience, of interest? Complex systems including molecules in condensed phases or biomolecules in cells can contain hidden heterogeneity produced by different local environments, different conformational states, or even different protein folds. Single-molecule studies allow us to explore hidden heterogeneity because we measure the distribution of behavior by recording the properties of each member of the ensemble, one by one. There are several specific ways single-molecule measurements can provide new information. Photochemistry or other photophysical changes in the immediate local environment can be detected as changes in resonant frequency, lifetime, or emission spectrum of the single molecule (spectral diffusion). We also obtain kinetic information from the time-dependent changes in the brightness of the molecule, or from the polarization changes that occur when the fluorophore rotates, or from the physical motion of the single-molecule label due to diffusion or transport. By measuring energy transfer between two different fluorophores, distance information on the 5-9 nm scale can be obtained. Many functional nanomachines present within cells operate one by one, thus the ability to observe single copies provides a new way to try to understand how the system works. In collaboration with the molecular biology and biochemistry communities, we work to discover how much can be learned with such single-molecule biophysical measurements. Our studies have explored various genetically encoded fluorescent proteins like GFP, kinesin molecular motors, Ca++ ion concentration sensors, chaperonins assisting protein folding, transmembrane proteins of the immune system in and out of living cells, and genetic regulatory proteins in bacteria. To enable further single-molecule imaging in cells, we are actively involved in the development of new photoswitchable single-molecule fluorophores. Single molecules also provide a window into a growing new field, nanophotonics. We have used a single molecule to make a quantum mechanical (non-Poissonian) light source operating at room temperature, and we have used nanoscale metallic electromagnetic structures to locally enhance light and therefore modify the interaction between light and single molecules. On a deeper level, 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 an off, it is possible to build up a superresolution image of the object under study, far beyond the optical diffraction limit. Several advanced techniques for obtaining three-dimensional information from single-molecule photoswitching are under development in the Moerner lab, especially the double-helix point spread function. Recently, we have built an Anti-Brownian ELectrokinetic (ABEL) trap which uses precision optical microscopy and active electrophoretic/electroosmotic feedback to grab and manipulate single nanoscale objects in solution for detailed optical measurements, without the need to attach the objects to a surface. We are actively applying this device to measure the optical dynamics of single antenna proteins and single redox enzymes in solution of importance to energy conversion and storage. I invite you to my group's home page for more information!

近期论文

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Gabriela S. Schlau-Cohen, Hsiang-Yu Yang, Tjaart P. J. Krüger, Pengqi Xu, Michal Gwizdala, Rienk van Grondelle, Roberta Croce, and W. E. Moerner, “Single-Molecule Identification of Quenched and Unquenched States of LHCII,” J. Phys. Chem. Lett. 6, 860-867 (2015). (: 10.1021/acs.jpclett.5b00034, published online February 18, 2015). Whitney C. Duim, Yan Jiang, Koning Shen, Judith Frydman, and W. E. Moerner, “Super-Resolution Fluorescence of Huntingtin Reveals Growth of Globular Species into Short Fibers and Coexistence of Distinct Aggregates,” ACS Chem. Biol. 9, 2767-2778 (2014) (: 10.1021/cb500335w, published online October 20, 2014). Mikael P. Backlund, Ryan Joyner, Karsten Weis, and W. E. Moerner, “Correlations of three-dimensional motion of chromosomal loci in yeast revealed by the double-helix point spread function microscope,” Mol. Biol. Cell 25 (22) 3619-3629 (2014) (: 10.1091/mbc.E14-06-1127, published online October 15, 2014). Matthew D. Lew and W. E. Moerner, “Azimuthal polarization filtering for accurate, precise, and robust single-molecule localization microscopy,” Nano Lett. 14, 6407-6413 (2014) (:10.1021/nl502914k, published online October 1, 2014). Marissa K. Lee, Prabin Rai, Jarrod Williams, Robert J. Twieg, and W. E. Moerner, “Small-Molecule Labeling of Live Cell Surfaces for Three-Dimensional Super-Resolution Microscopy,” J. Amer. Chem. Soc. 136, 14003-14006 (2014) (: 10.1021/ja508028h, published online, September 15, 2014) Yoav Shechtman, Steffen J. Sahl, Adam S. Backer, and W. E. Moerner, “Optimal Point Spread Function Design for 3D Imaging,” Phys. Rev. Lett. 113, 133902 (2014), (: 10.1103/PhysRevLett.113.133902, published online September 26, 2014) Yin Loon Lee, Joshua Santé, Colin J. Comerci, Benjamin Cyge, Luis F. Menezes, Feng-Qian Li, Gregory G. Germino, W. E. Moerner, Ken-Ichi Takemaru, and Tim Stearns, “Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole–cilium interface and facilitates proper cilium formation and function,” Mol. Biol. Cell 25 (19) 2919-2933 (2014) (: 10.1091/mbc.E14-02-0735, published online August 7, 2014.) Adam S. Backer and W. E. Moerner, “Extending Single-Molecule Microscopy Using Optical Fourier Processing,” James Skinner Festschrift, J. Phys. Chem. B 118, 8313-8329 (2014) (: 10.1021/jp501778z, published online 18 April 2014). A. S. Backer, M. P. Backlund, A. R. von Diezmann, S. J. Sahl, and W. E. Moerner, “A bisected pupil for studying single-molecule orientational dynamics and its application to 3D super-resolution microscopy,” Appl. Phys. Lett. 104, 193701 (5) (2014). Christopher P. Calderon, Lucien E. Weiss, and W. E. Moerner, “Robust hypothesis tests for detecting statistical evidence of two-dimensional and three-dimensional interactions in single-molecule measurements,” Phys. Rev. E 89, 052705(8) (2014) (: 10.1103/PhysRevE.89.052705, published online 12 May 2014). Gabriela S. Schlau-Cohen, Samuel Bockenhauer, Quan Wang, and W. E. Moerner, “Single-molecule spectroscopy of photosynthetic proteins in solution: exploration of structure–function relationships,” Minireview, Chem. Sci. 5, 2933-2939 (:10.1039/C4SC00582A, published online 15 April 2014). Jerod L. Ptacin, Andreas Gahlmann, Grant R. Bowman, Adam M. Perez, Alexander R. S. von Diezmann, Michael R. Eckart, W. E. Moerner, and Lucy Shapiro, “Bacterial scaffold directs pole-specific centromere segregation,” Proc. Nat. Acad. Sci. (USA) 111, E2046-E2055 (2014) (:10.1073/pnas.1405188111, published online 28 April 2014). Quan Wang and W. E. Moerner, “Single-molecule motions enable direct visualization of biomolecular interactions in solution,” Nature Methods 111, 555-558 (published online March 9, 2014). Quan Wang and W. E. Moerner, “Spectroscopic and transport measurements of single molecules in solution using an electrokinetic trap,” Proc. SPIE 8950, 895004 1-10 (2014). Adam S. Backer, Mikael P. Backlund, Matthew D. Lew, Alexander R. Diezmann, Steffen J. Sahl, and W. E. Moerner, “Single-molecule orientation measurements with a quadrated pupil,” Proc. SPIE 8950, 89500L 1-6 (2014). Samuel D. Bockenhauer, Thomas M. Duncan, W. E. Moerner and Michael Börsch, “The regulatory switch of F1-ATPase studied by single-molecule FRET in the ABEL Trap, ” Proc. SPIE 8950, 89500H 1-14 (in press, 2014). Mikael P. Backlund, Matthew D. Lew, Adam S. Backer, Steffen J. Sahl, and W. E. Moerner, “The role of molecular dipole orientation in single-molecule fluorescence microscopy and implications for super-resolution imaging,” Minireview, ChemPhysChem 15, 587-599 (2014), published online December 30, 2013. Andreas Gahlmann and W. E. Moerner, “Exploring bacterial cell biology with single-molecule tracking and super-resolution imaging,” Nature Reviews Microbiology 12, 9-22 (2014), published online December 16, 2013. Christopher P. Calderon, Michael A. Thompson, Jason M. Casolari, Randy C. Paffenroth, and W. E. Moerner, “Quantifying Transient 3D Dynamical Phenomena of Single mRNA Particles in Live Yeast Cell Measurements,” J. Phys. Chem. B 117, 15701-15713 (2013), published online September 9, 2013. Steffen J. Sahl and W. E. Moerner, "Super-resolution Fluorescence Imaging with Single Molecules,” Curr. Opin. Struct. Biol. 23, 778-787 (2013), published online 8 August 2013.