The David L. Weaver Endowed Lecture Series in Biophysics and Computational Biology is dedicated to the memory of David L. Weaver, a prominent biophysics researcher and professor at Tufts University.
About Dr. Weaver
Dr. Weaver made significant contributions to the understanding of protein folding. He was impressed with the research and faculty at the UC Davis Genome Center, where he was planning to spend his sabbatical year 2006–2007.
Dr. Weaver focused his early research on high-energy physics, studying photon production and elementary particles. After spending a year and a half as a NATO Fellow at the European Center for Nuclear Research (CERN), in Geneva, Switzerland, he returned to Tufts and began to think about how he could apply his physics background to problems in biology. While he continued to make significant contributions in high-energy physics, for which he received tenure at Tufts in 1969, Dr. Weaver’s interests continued to shift towards some of the key unsolved problems in biology. At the University of Rome, Italy, as a visiting CNN Fellow at the Frascati National Laboratory, he became more and more interested in applying his mathematical skills to gain a better understanding of molecular dynamics. He visited Dr. Martin Karplus at Harvard during a sabbatical in 1972, and they began a collaboration that culminated in a paper about a then theoretical diffusion-collision model for protein folding (Nature, 1976). The Diffusion-Collision Model was ahead of its time because the data needed to test it were not available when it was published in 1976. But by the mid-1990s experimental studies had shown that the model did indeed describe the folding mechanism of many proteins. The field has been completely transformed in recent years because of its assumed importance for understanding the large number of protein sequences available from genome projects, says Karplus, and because of the realization that misfolding can lead to a wide range of human diseases.
Dr. Weaver received grants from NASA, NATO, Bruker Optics, and the NIH to establish computer facilities at Tufts where he continued to work with students, Dr. Karplus and other collaborators to improve his understanding of important biophysical problems. He was a regular visitor at labs overseas and in the United States, and he authored or co-authored a number of significant scientific publications.
He held degrees in Chemistry from Rensselaer Polytechnic Institute and in Physical Chemistry from Iowa State University. A Fellow of the American Physical Society, Dr Weaver also served as the chair of the Tufts Department of Physics and Astronomy from 1989 to 2002. He was born in Albany, NY, on April 18th, 1937.
David Weaver possessed an easy manner, a sense of fairness, curiosity and an enjoyment of life that was evident in his teaching and relations with colleagues. All who knew him will miss his kind and cheerful humor, his smile and his generous spirit.
The 2018 Lecture: Professor Xiowei Zhuang —‘Illuminating Biology at the Nanoscale and Systems Scale by Imaging‘
Date: Wednesday, April 25th 2018, 3pm, GBSF 1005.
Understanding the inner workings of a cell requires imaging techniques with molecular-scale resolution. Developing such techniques is the long-standing goal of Xiaowei Zhuang’s research. Her laboratory invented STORM, a single-molecule-based super-resolution fluorescence microscopy method with which they were able to achieve three-dimensional super-resolution imaging of a variety of biological systems, ranging from single-cell organisms to complex brain tissues. These studies led to the discovery of many novel cellular structures, such as the periodic membrane skeletons in the axons of neurons. The Zhuang laboratory also invented a single-cell transcriptome imaging technique, MERFISH, which allows numerous RNA species to be imaged and quantified in single cells in their native context. They also use those imaging methods to study how proteins and nucleic acids interact, how viruses infect cells, and how neurons compute.
Dissecting the inner workings of a cell requires imaging methods with molecular specificity, molecular-scale resolution, and dynamic imaging capability such that molecular interactions inside the cell can be directly visualized. However, the diffraction-limited resolution of light microscopy is substantially larger than molecular length scales in cells, making many sub-cellular structures difficult to resolve. Another major challenge in imaging is the relatively low throughput in terms of the number of molecular species that can be simultaneously imaged, while genomic-scale throughput is desired for investigating many systems level questions. In this talk, I will describe two imaging methods that overcome these challenges and their biological applications. I will first describe stochastic optical reconstruction microscopy (STORM), a super-resolution imaging method that overcomes the diffraction limit. This approach has allowed multi-color and three-dimensional imaging of living cells with nanometer-scale resolution. I will present both technological advances and biological applications of STORM, with focus on some recent discoveries of novel sub-cellular structures enabled by STORM. I will also describe our recently developed single-cell transcriptome imaging method, multiplexed error-robust FISH (MERFISH), which allows thousands of RNA species to be quantified in a spatially resolved manner in individual cells. This approach enables single-cell transcriptomic analysis in the native context of tissues, facilitating the delineation of gene regulatory networks, the mapping of RNA distributions inside cells, and the mapping of distinct cell types in complex tissues. In addition, multiplexed FISH allowed us to trace the folding path of individual chromosomes, which has provided novel insights into the 3D organization of the genome.
About Xiaowei Zhuang
Dr. Zhuang received her B.S. degree in Physics from the University of Science and Technology of China, Ph.D. Degree in Physics from the University of California at Berkeley, and postdoctoral training in biophysics at Stanford University. In 2001, she became an assistant professor at Harvard University, where she was promoted to associate professor in 2005 and full professor in 2006. She joined the Howard Hughes Medical Institute as an investigator in 2005. Zhuang is a member of the National Academy of Sciences, a fellow of American Association of the Advancement of Science, and a fellow of the American Physical Society
Emanuel G, Moffitt JR, Zhuang X. High-throughput, image-based screening of pooled genetic-variant libraries. Nat Methods. 2017;14: 1159–1162.
Han B, Zhou R, Xia C, Zhuang X. Structural organization of the actin-spectrin-based membrane skeleton in dendrites and soma of neurons. Proc Natl Acad Sci U S A. 2017;114: E6678–E6685.
Chung J-J, Miki K, Kim D, Shim S-H, Shi HF, Hwang JY, et al. CatSperζ regulates the structural continuity of sperm Ca2+signaling domains and is required for normal fertility. Elife. 2017;6. doi:10.7554/eLife.23082
Beliveau BJ, Boettiger AN, Nir G, Bintu B, Yin P, Zhuang X, et al. In Situ Super-Resolution Imaging of Genomic DNA with OligoSTORM and OligoDNA-PAINT. In: Erfle H, editor. Super-Resolution Microscopy: Methods and Protocols. New York, NY: Springer New York; 2017. pp. 231–252.
Wang S, Su J-H, Beliveau BJ, Bintu B, Moffitt JR, Wu C-T, et al. Spatial organization of chromatin domains and compartments in single chromosomes. Science. 2016;353: 598–602.
Wang S, Su J-H, Zhang F, Zhuang X. An RNA-aptamer-based two-color CRISPR labeling system. Sci Rep. 2016;6: 26857.
Bates M, Jones SA, Zhuang X. Stochastic optical reconstruction microscopy (STORM): a method for superresolution fluorescence imaging. Cold Spring Harb Protoc. 2013;2013: 498–520.
Rust MJ, Bates M, Zhuang X. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat Methods. Nature Publishing Group; 2006;3: 793.
The endowed lecture series was established by David’s family, just one of many ways in which people have helped make a difference in advancing UC Davis’s commitments to teaching, research, and public service.
- 2017: Professor Angela M. Gronenbron, Structural Biology, University of Pittsburgh. Synergy between NMR, cryo-EM and large-scale MD simulations – An all atom model of a native HIV capsid. (video)
- 2016: Professor Sir Tom Blundell, Biochemistry, University of Cambridge. Biophysics, Computational Biology and the Discovery of New Medicines: The Emergence of Resistance in Cancer and Tuberculosis. (video)
- 2015: Professor Stephen Quake, School of Engineering, Stanford University and Howard Hughes Medical Institute. Single Cell Genomics. (video)
- 2014: Professor Arup Chakraborty, Laboratory for Computational Immunology, Massachusetts Institute of Technology. How to Hit HIV Where It Hurts.
- 2013: Professor Joanna Aizenberg, Harvard University, School of Engineering and Applied Science. Novel Biomimetic ‘Spiny’ Surfaces in Medical Applications.
- 2012: Professor Cheryl Arrowsmith, Structure Genomic Consortium, Department of Medical Biophysics, University of Toronto. Structural and Chemical Biology of Epigenetic Regulators.
- 2011: Professor John Kuriyan, Chancellor’s Professor, Department of Molecular and Cell Biology and Department of Chemistry, University of California, Berkeley. Molecular Mechanisms in Signal Transduction by Tyrosine Kinases.
- 2010: Professor Susan Lindquist, Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Broad Institute of MIT and Harvard Department of Biology, MIT. Protein Folding Driving the Evolution of Genomes.
- 2009: Professor Gregory Petsko, Gyula and Katica Tauber Professor, Department of Biochemistry and Chemistry, Brandeis University, Adjunct Professor, Department of Neurology and Center for Neurological Diseases, Harvard Medical School. Structural Neurology: Understanding, Treating and Preventing Neurodegenerative Diseases.
- 2008: Professor Christopher Dobson, John Humphrey Plummer Professor of Chemical and Structural Biology, Master of St. Johns College, Cambridge University, United Kingdom. Life on the Edge: The Nature and Origins of Protein Misfolding Diseases.
- Invited guest speaker, Professor Rohit Pappu, Washington University, A Student’s Remembrance of David Weaver.
- 2007: Professor Martin Karplus, Laboratoire de Chimie Biophysique, ISIS, Universite Louis Pasteur and Department of Chemistry and Chemical Biology, Harvard University, 2013 Nobel Prize in Chemistry, How Proteins Work: Insights from Simulations.
- Opening remarks by Dirk Laukien, Ph.D., Senior Scientific Fellow, Bruker Optics, Unfolding David Weaver’s Contributions at Bruker Optics.