Speaker bios and abstracts

Dr. Sunney Xie

Bio: Sunney Xie came to Harvard in 1999 from his post as chief scientist for the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory, where he began his work on single-molecule reactions. Xie also served as adjunct professor of physics at Portland State University in Portland, Ore.

Xie, 37, was born in Beijing, the son of two chemists, both professors at Peking University. With chemists as parents, Xie said it seemed a natural choice for him to enter the field. Xie must have become comfortable in the company of chemists because his wife, Lin Song, is also a chemist.

He received a bachelor’s degree in chemistry from Beijing University in 1984 and then came to the United States to further his studies. He received a doctorate in chemistry in 1990 from the University of California at San Diego. After leaving San Diego, Xie went to the University of Chicago, where he did two years of postdoctoral work.

In 1992, he became a senior research scientist in the Environmental Molecular Sciences Laboratory, a post he held until 1995, when he became chief scientist there.

Xie is excited to be at Harvard. He enjoys teaching students and working with them to take single molecule and imaging work to the next level. Growing up in a house headed by two chemistry professors, Xie said he has always been fond of the academic lifestyle.

Xie has published many articles and spoken at numerous conferences and universities. He is on the editorial boards of three scientific journals. In 1996, Xie’s work on single-molecule spectroscopy won him the Coblentz Award, which is given each year to an outstanding molecular spectroscopist under the age of 36, by the Coblentz Society.

Talk title: Living cells as test tubes: Biochemistry and molecular biology through advanced optical microscopy

Abstract: The combination of specific probes and advanced optical microscopy now allows quantitative probing of biochemical reactions in living cells. On selected systems, one can detect and track a particular protein with single-molecule sensitivity, nanometer spatial precision, and millisecond time resolution. Metabolites, usually difficult to detect, can be imaged and monitored in living cells with coherent anti-Stokes Raman scattering microscopy. The application of these techniques in studying gene expression, active transport, and lipid metabolism will be described.

Dr. Wolfgang Baumeister

Bio: Wolfgang Baumeister studied biology, chemistry and physics at the Universities of Muenster and Bonn, Germany, and he obtained his Ph.D. from the University of Düsseldorf in 1973. He spent time at the Cavendish Laboratory in Cambridge, England, and in 1978 became a lecturer in biophysics. In 1983 Wolfgang moved to the Max-Planck Institute of Biochemistry in Martinsried, Germany, where he became director and head of the department of Structural Biology in 1988. He is also an Honorary Professor of Physics at the Technical University of Munich. Wolfgang combines novel electron microscopy approaches with molecular biology and biochemistry to study the macromolecular machinery for cellular protein quality control.

Wolfgang is the recipient of numerous prizes including the Otto Warburg Medal, Schleiden-Medal, Louis-Jeantet Prize for Medicine, Stein and Moore Award, and Harvey-Prize in Science and Technology. He is a member of several academies including the American Academy of Arts & Sciences.

Talk title: Exploring the inner space of cells by cryoelectron-tomography

Abstract: Electron tomography is uniquely suited to obtain three-dimensional images of large pleiomorphic structures, such as supramolecular assemblies, organelles or even whole cells. With the advent of automated data acquisition, facilitated by technological advances (computer-controlled electron microscopes and large area CCD cameras), it has become possible to examine frozen-hydrated samples in a close-to-life state under non-critical electron dose conditions and to attain resolutions which allow the docking of high resolution component structures. High-resolution tomograms of organelles or cells are essentially 3-D images of the cell’s entire proteome and should ultimately enable us to map the spatial relationships of macromolecules in a functional cellular context. However, it is no trivial task to retrieve this information because of the poor signal-to-noise ratio of such tomograms and the crowded nature of the cytoplasm and many organelles. Denoising procedures can help to combat noise and to facilitate visualization, but advanced pattern recognition methods are needed for detecting and identifying with high fidelity specific macromolecules based on their structural signature (size and shape).

Experiments with phantom cells, i.e. lipid vesicles encapsulating a known set of proteins have shown that such a template-matching approach is feasible. Once the challenges of obtaining sufficiently good resolution and of creating efficient data-mining algorithms are met, and comprehensive libraries of template structures become available, we will be able to map the supramolecular landscape of cells systematically and thereby provide a new perspective for analyzing the molecular interaction networks underlying higher cellular functions.

Dr. Douglas Koshland

Bio: Dr. Koshland is an Investigator of the Howard Hughes Medical Institute and Senior Staff Member in the Department of Embryology at the Carnegie Institution of Washington, Baltimore. He earned his B.A. degree from Haverford College and his Ph.D. degree in microbiology with David Botstein at the Massachusetts Institute of Technology, where he studied the secretion of beta-lactamase in Salmonella typhimurium. Postdoctoral work was done with Leland Hartwell at the University of Washington, Seattle, where he studied yeast chromosome segregation in vivo, and with Marc Kirschner at the University of California, San Francisco, where he studied vertebrate kinetochore function in vitro.

Talk title: Visualizing yeast chromosomes, an oxymoron?

Abstract: The conversion of eukaryotic chromosomes from their disperse state in interphase to their highly compacted form in mitosis was first documented by images from Flemming around the turn of the last century. For almost a century these images beg the question, how is higher order chromosome structure achieved. Indeed it was thought that the mechanism of higher order folding of chromosomes might not be conserved since chromosomes appeared very different in mitotic images from various organisms. That this was not the case came through the discovery in our laboratory and others that higher order chromosome folding was mediated by a conserved set of SMC complexes. Other studies show that SMC complexes organize the three dimensional architecture of chromosomes in recombination, DNA repair, and transcription as well as mitosis. The mechanism of action of SMC complexes again has been driven by an image. Electron micrographs of these complexes reveal their potential to form very large rings, 80 nm in circumference. The blessing and the curse of such a powerful image will be discussed and how this image eventually lead our lab to develop hybrid yeast as a model for genome evolution.

Dr. Karel Svoboda

Bio: Karel Svoboda received a B.A. in physics from Cornell University and a Ph.D. in biophysics from Harvard University. He did postdoctoral work at Bell Laboratories and spent eight years at Cold Spring Harbor Laboratory before moving to HHMI’s Janelia Farm Research Campus. He uses biophysical tools to explore the synaptic and circuit mechanisms of learning in the mammalian cortex.

Talk title: Imaging the function and plasticity of single synapses

Abstract: Which neocortical elements change in response to novel sensory experience? Which elements are stable and how are they maintained? Answers to these questions are fundamental to the cell biological mechanisms of plasticity and the memory capacity of the brain. Our approach has been to image plasticity of individual synapses in the adult mouse brain in vivo.

We find that that neurons display a rich, cell-type specific, repertoire of micrometer-level structural plasticity of dendritic spines, axonal terminals, and axonal branch tips over days. By combining in vivo imaging with retrospective electron microscopy and physiological analysis we have found that synapse formation and elimination at specific projections underlies experience-dependent rewiring of neocortical circuits.

A subset of excitatory synapses in the neocortex can persist for months to years. To analyze the mechanisms of this stability we have developed optical methods to measure the trafficking of synaptic proteins in vivo. Remarkably, synapses compete for a common pool of highly dynamic synaptic molecules, with time-constants of ~ 1 hour. How then is long-term stability achieved? We show that the kinetic interactions of synaptic proteins with individual synapses are intricately tuned in a synapse-specific manner to maintain synaptic stability. Finally, we have used fluorescence lifetime imaging combined with 2-photon microscopy to image the signal- transduction pathways underlying plasticity in individual synapses.

Alice Ting

Bio: Alice Ting received her undergraduate degree in chemistry from Harvard, working with synthetic chemist E. J. Corey. She then moved to Berkeley for her Ph.D. training, working on unnatural amino acid mutagenesis and single molecule spectroscopy with Peter Schultz. Alice did her postdoctoral work at UCSD with Roger Tsien on FRET reporters for imaging kinase activities in cells. She started her own lab at MIT in July of 2002 and has built a research program at the interface of chemistry and biology, focused on the development of new methodology for studying protein function and trafficking in living cells. She has received a number of awards, including the McKnight Technological Innovations in Neuroscience Award, the Sloan Foundation Research Fellowship, the Office of Naval Research Young Investigator Award, the NIH Career Development Award, and the Camille Dreyfus Teacher-Scholar Award. Alice was recently named to MIT’s TR35 (a list of 35 young innovators under 35 with this year's best ideas).

Talk title: New methodology for imaging protein trafficking and function in living cells

Abstract: GFP is an extremely useful protein tag for cell biology, but it is large, relatively dim, photobleaches readily (making it unsuitable for single molecule imaging), and can only be visualized by optical microscopy. Our group has developed new methodology for labeling cellular proteins with small organic fluorophore as well as quantum dots. These methods make use of the incredible specificity of natural enyzmes such as biotin ligase. We will describe the development of these new protein labeling tools as well as their application to cell biological problems such as clathrin-mediated endocytosis and synaptogenesis.

Dr. Ulrich von Andrian

Bio: Uli von Andrian received his M.D. and Ph.D. from Ludwig-Maximilians University in Munich, Germany. He did postdoctoral work at the La Jolla Institute for Experimental Medicine in California. He then went onto Harvard in 1994 as an assistant professor of pathology at HMS, and junior investigator at CBR Institute for Biomedical Research. He is currently professor of pathology at HMS, and senior investigator at CBR Institute. Uli is a member of the European Academy of Sciences and the American Society for Cell Biology, and in 2004 he was awarded the Amgen Outstanding Investigator Award.

Talk title: Visualizing the immune response

Abstract: Cell migration and coordinated cell-cell interactions are hallmarks features of the immune system. Recent advances in real-time in vivo imaging technology have added a new dimension to our efforts to understand the dynamics and complex interplay of the key cellular players in the steady state and during ongoing immune responses. In particular, multiphoton intravital microscopy (MP-IVM) allows prolonged three-dimensional observations of highly dynamic events that occur hundreds of micrometers below the surface of solid tissues in living animals. Using a newly developed MP-IVM model in mouse popliteal lymph nodes, we have analyzed how CD8 T cells are activated and how they interact with tumor antigen-presenting target cells in the presence and absence of CD4+CD25+ regulatory T cells (Treg). We observed that the inital activation (priming) of naive T cells occurs in three distinct interactive phases characterized by a several hours-lasting period of short serial contacts followed by a phase of tight, sustained clustering, which after the first day converts to a prolonged period during which the activated T cells are highly motile, engage in short contacts with antigen-presenting cells and proliferate rapidly. Several days later, the activated T cells differentiate into full-fledged cytotoxic T lymphocytes (CTL), whose ability to kill antigen-presenting target cells can be studied by MP-IVM. We found that CTL without Treg killed their targets at a faster rate than regulated CTL. Our experiments indicate that Treg suppress CTL-mediated adaptive immunity by creating a local milieu that permits the acquisition of effector potential, but withholds the license to kill.

Dr. Xiaowei Zhuang

Bio: Xiaowei Zhuang received her B.S. degree in Physics from the University of Science and Technology of China, and her Ph.D. Degrees in Physics from University of California at Berkeley. In 2001, she joined the faculty of Harvard University where she was promoted to associate professor in 2005 and full professor in 2006. She is currently a Professor of Chemistry and Chemical Biology and a Professor of Physics at Harvard University and an investigator of the Howard Hughes Medical Institute.

Interests of the Zhuang research lab focus on single-molecule biophysics and live cell imaging. In particular, members of the Zhuang lab use various single-molecule approaches to study RNA-protein interactions and ribonucleoprotein enzymes. They are investigating the infection mechanism of various medically important viruses by imaging the behavior of individual virus particles in live cells. Xiaowei Zhuang has received numerous awards including the Pure Chemistry Award, Camille Dreyfus Teacher-Scholar Award, Alfred P. Sloan Research Fellowship, MIT TR100 Young Innovators Award, MacArthur Fellowship, the Packard Fellowship for Science and Engineering, etc.

Talk title: Imaging cellular processes at high resolution

Abstract: As we enter the post-genomic era and as biology gets increasingly quantitative, a comprehensive understanding of biological processes at the molecular level is becoming more readily accessible. However, severe roadblocks still exist, among which is the challenge that we face in characterizing the complex dynamics of biological processes. To tackle this problem, we are exploring optical imaging techniques to monitor, in real-time, the behavior of individual biological molecules and complexes, both in vitro and in live cells. This approach allows complex dynamics to be directly and unambiguously observed. By combining the dynamic information obtained at the single-molecule (or single-complex) level with structural and biochemical analyses, we create “molecular movies” of biological processes to obtain mechanistic understandings of these processes. In this talk, I will discuss our recent progress on the studies of viral entry and viral protein function by live-cell and single-molecule imaging. I will also present a new high-resolution optical microscopy technique with nanometer imaging resolution.

Last updated September 28, 2006.