2017 David L. Weaver Lecture: Monday April 3rd, 3pm, GBSF 1005

david_weaverOverview

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 2017 Lecture: Professor Angela M. Gronenbron —‘Synergy between NMR, cryo-EM and large-scale MD simulations – An all atom model of a native HIV capsid’

Date: Monday, April 3rd 2017, 3pm, GBSF 1005.

HIV and other retroviruses use a Trojan horse style of infection, taking advantage of a cloak that shields its genome till the time is ripe to open the shield. Once HIV gets inside the cell, it takes over the cellular machinery, turning it into a factory for its own reproduction. This entails a derailment of the normal host defense pathways, rendering HIV resistant to cell-mediated destruction responses. In mature HIV-1 particles a conical-shaped capsid core encloses the viral RNA genome. Previous structural analysis of two- and three-dimensional arrays provided a molecular model of the capsid protein (CA) hexamer and revealed three interfaces in the lattice. Using the high-resolution NMR structure of the CA C-terminal domain (CTD) dimer and in particular the unique interface identified, it was possible to reconstruct a model for a tubular assembly of CA protein that fit extremely well into the cryoEM density map. A novel CTD-CTD interface at the local three-fold axis in the cryoEM map was confirmed by mutagenesis to be essential for function. More recently, the cryo-EM structure of the tube was solved at 8Å resolution and this cryo-EM structure allowed unambiguous modeling and refinement by large-scale molecular dynamics (MD) simulation, resulting in all-atom models for the hexamer-of-hexamer and pentamer-of-hexamer elements of spheroidal capsids. Furthermore, the 3D structure of a native HIV-1 core was determined by cryo-electron tomography (Cryo-ET), which in combination with MD simulations permitted the construction of a realistic all-atom model for the entire capsid, based on the 3D authentic core structure.
 

 

About Angela M. Gronenborn

 

Dr. Gronenborn received her Diploma (1975) and Doctoral (1978) degrees in Chemistry from the University of Cologne, Germany. After post-doctoral work with Jim Feeney at The National Institute for Medical Research in Mill Hill, London, UK she continued her research at NIMR in the Division of Physical Biochemistry. In 1984 she moved to the Max Planck Institute of Biochemistry in Martinsried (Munich) as head of the biological NMR group. In 1988 she relocated to the Laboratory of Chemical Physics in NIDDK at the National Institutes of Health in Bethesda, where together with Bax and Clore she was instrumental in developing NMR methodologies for biological macromolecules. Since 2005 she is a Professor at the University of Pittsburgh Medical School where she currently holds the UPMC Rosalind Franklin Chair in Structural Biology and, in 2011, was named Distinguished Professor of Structural Biology. She was elected to the National Academy of Sciences and the Norwegian Academy of Science and Letters in 2007 and 2010 respectively. In 2014, she received the Life Science Award from the Carnegie Science Center and was also elected to the Germany Academy of Sciences, Leopoldina.

Key contributions include the development of restrained molecular dynamics/simulated annealing algorithms and multidimensional, heteronuclear spectroscopic methods, which allowed the extension of conventional NMR methods to higher molecular weight systems. Dr. Gronenborn has solved solution structures of a large number of medically and biologically important proteins, including cytokines and chemokines, transcription factors and their complexes and various HIV and AIDS related proteins. Her extensive bibliography contains more than 470 articles and numerous book chapters.

Key publications:

Gronenborn AM, Birdsall B, Hyde EI, Roberts GCK, Feeney J, Burgen ASV.  Direct observation by NMR of two coexisting conformations of an enzyme-ligand complex in solution.  Nature 230, 273 (1980).

Oschkinat H, Griesinger C, Kraulis PJ, Sørensen OW, Ernst RR, Gronenborn AM, Clore GM. Three-dimensional NMR spectroscopy of a protein in solution. Nature 332, 374 (1988).

Clore GM, Gronenborn AMStructures of larger proteins in solution: three- and four-dimensional heteronuclear NMR spectroscopy. Science 252, 1390 (1991).

Omichinski JG, Clore GM, Schaad O, Felsenfeld G, Traino, C, Appella E, Stahl SJ, Gronenborn AM.   NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science 261, 438-446 (1993).

Frank MK, Dyda F, Dobrodumov A, Gronenborn AMCore mutations switch monomeric protein GB1 into an intertwined tetramer.  Nat. Struct. Biol., 9(11): 877-885 (2002).

Byeon, IL, Meng X, Jung J, Zhao G, Yang R, Ahn J, Shi J, Concel J, Aiken C, Zhang P, Gronenborn AM. Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell 139, 780 (2009). PMC2782912

Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics.  Nature 497, 643 (2013).  PMC3729984

 

Giving Opportunities

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.

Previous Lectures

  • 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.
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Upcoming Talks and Events

Events on January 14, 2019
WCMC: Hands-on LC-MS Data processing and Statistics
Starts: 12:00 am
Ends: January 19, 2019 - 12:00 am
Location: UC Davis Conference Center, 550 Alumni Ln, Davis, CA 95616, USA
Description: Registration: http://ucanr.edu/survey/survey.cfm?surveynumber=15575

This course will feature hands-on training with real-world metabolomics data covering LC/MS compound identification, data processing, statistical analysis, network mapping and data interpretation.

We will instruct using a variety of software, workflows, and algorithms but also give theoretical background information and overviews. We will focus on utilizing open source software and only refer to commercial or vendor software when necessary.

All participants will be trained on laptops that were specifically purchased for course training, with all software already installed and data available to use.

The course will include:

untargeted data processing and exercises on MS-DIAL software (in comparison to XCMS)
exercises on identification of unknowns by cheminformatics software workflows (incl MS-FINDER, CFM-ID, and various databases and small software routines)
data normalization and transformation with and without internal standards and quality controls
multivariate and univariate statistics (incl MetDA in comparison to MetaboAnalyst)
pathway mapping (incl MetaBox consisting of MetDA, ChemRICH and MetaMapp in comparison to MetaboAnalyst)
The course fees are $ 2,500 per participant to cover expenses for instructors, organization, materials and meals.

more Info:

Jeannette Martins

email: jmartins@ucdavis.edu

phone: +1-530-754-5357

Cancellation policy
Requests for refunds will be honored when received 2 month prior to the program. Refund requests can be only accepted in a written form. However, another person may be substituted at any time for this program, unless it requires issuing a new travel visa for international scholars.

A $150 administrative fee and the credit card fee will be deducted for cancellations.
In the unlikely event that this program is cancelled or postponed due to insufficient enrollments or unforeseen circumstances, the WCMC will fully refund registration fees but cannot be held responsible for any other expenses, including cancellation or change charges assessed by airlines, hotels, travel agencies, or other organizations.
Events on May 16, 2019
WCMC: Best practice in operating mass spectrometers in Metabolomics
Starts: 12:00 am
Ends: May 20, 2019 - 12:00 am
Location: Genome and Biomedical Sciences Facility, 451 Health Science Dr, Davis, CA 95616, USA
Description: Registration: https://goo.gl/forms/TGeuALrTMfTpGh0O2

This course will enhance your standing and expertise to prepare and successfully run samples in a metabolomic laboratory. It is designed to provide hands-on practical exercises using gas and liquid chromatography coupled to mass spectrometry (GC-MS & LC-MS). The course will focus on untargeted data acquisition in metabolomics with both nominal mass and accurate mass instruments. You will learn how to operate the instruments, how to collect metabolite profiles on complex samples and how to prepare and derivatize samples, troubleshoot instruments, acquire data and perform data quality control routines (QA/QC). Overall, you will receive comprehensive understanding of the current best practices in the metabolomics laboratory.

The course will include:


1. Fundamentals of mass spectrometry, chromatography, and metabolomics.
2. hands-on exercises on sample preparation, including extraction and derivatization
of complex samples for untargeted metabolomics profiling
3. Hands-on exercises to learn how to operate both gas and liquid chromatography
coupled to mass spectrometry (GC-MS & LC-MS).
4. quality control routines (QA/QC) in order to ensure comparable data, reproducibility, and instrument performance.
Events on August 19, 2019
International Summer Sessions in Metabolomics
Starts: 12:00 am
Ends: August 31, 2019 - 12:00 am
Location: UC Davis Alumni Center
Description: Registration: https://docs.google.com/forms/d/e/1FAIpQLSeVnMXxhkMtlET-RGDgW99jA3lr1wS4hypU0kI6O1yGV0GqBg/viewform?usp=sf_link

Contact: Jeannette Martins jmartins@ucdavis.edu

Please, contact us now if you need letters of support to obtain funding from your home institutions.

The West Coast Metabolomics Center organizes an instructional course for researchers for researcher which need a deeper and broader understanding in the field of Metabolomics. This course will span 12 days from August 19-30, 2019.

In order to serve the group interests best and have interesting open discussions we have a small class of 22 participants. The participants come always from all over the world and have a very diverse research background.

The course will include:

study design, including pitfall analysis and hidden biases in studies from microbial, plant, mouse and human cohort research
sample preparation and quality control
in-laboratory detailed discussions standard operating procedures for GC-MS and LC-MS data acquisitions
targeted metabolomics, including monitoring charts and use of isotope labeled internal standards
exercises on flux analysis in cancer cells by isotope tracer analysis
untargeted data processing and exercises on MS-DIAL software (in comparison to XCMS)
exercises on identification of unknowns by cheminformatics software workflows (incl MS-FINDER, CFM-ID, and various databases and small software routines)
data normalization and transformation with and without internal standards and quality controls
multivariate and univariate statistics (incl MetDA in comparison to MetaboAnalyst)
pathway mapping (incl MetaBox consisting of MetDA, ChemRICH and MetaMapp in comparison to MetaboAnalyst)
Past course participation:
2018 course: 25 researchers from USA, Brazil, China, Japan, Korea, Taiwan, Russia, Norway, Germany, Poland, Canada
2017 course: 24 researchers from USA, Saudi-Arabia, China, , Korea, Italy, Denmark, Iran, United Kingdom
2016 course: 23 researchers from USA, Saudi-Arabia, China, Thailand, Japan, Italy, Brazil, Chile, Korea, and Canada.
2015 course: 21 researchers from USA, China, Germany, Brazil, Switzerland, Denmark, Canada, Korea, Malaysia, and Netherlands.
2014 course: 20 researchers from USA, New Zealand, Italy, Denmark, China, Canada, Turkey and Switzerland
2013 course: 20 researchers from USA, New Zealand, Costa Rica, Denmark, Luxembourg, Brazil, Columbia, Japan, Korea and Taiwan.
For questions, please contact our program representative Jeannette Martins (jmartins@ucdavis.edu).

Visiting Scientists
Participation in this course is mandatory for visiting international researchers who want to engage in collaborative research projects.
The minimum time span for such collaborative visits is 3 months, preferred is 12 months.
An additional payment of $500 for the visa has to be paid prior to arrival at UC Davis.

Each year, up to five international researchers have started such research visits, funded by agencies in their home countries.
Please contact us at least 6 months in advance to help you with letters of support, booking your course, and obtaining a visa for you.
Cancellation policy
Requests for refunds will be honored when received 2 month prior to the program. Refund requests can be only accepted in a written form. However, another person may be substituted at any time for this program, unless it requires issuing a new travel visa for international scholars.

A $150 administrative fee and the credit card fee will be deducted for cancellations.
In the unlikely event that this program is cancelled or postponed due to insufficient enrollments or unforeseen circumstances, the WCMC will fully refund registration fees but cannot be held responsible for any other expenses, including cancellation or change charges assessed by airlines, hotels, travel agencies, or other organizations.

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