About Dr. WeaverDr. 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 2006â2007. 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 2016 Lecture:Â Professor Sir Tom BlundellÂ â'Biophysics, Computational Biology and the Discovery of New Medicines: The Emergence of Resistance in Cancer and Tuberculosis'
Over the past fifty years our knowledge of the evolution of proteins in living cells has been mapped in terms of amino acid sequence and molecular architecture. Second generation methods of gene sequencing are now allowing us to follow the emergence of resistance as tumours and pathogens such as Mycobacterium tuberculosis and HIV evolve to evade the immune response of the host and resist potent new medicines. I will discuss work inÂ my laboratory, funded by the Wellcome Trust on cancer and by the Gates Foundation on tuberculosis. I will describe biochemical, biophysical, bioinformatics and computational techniques that contribute to a multidisciplinary approach to drug discovery, known as fragment-based drug discovery. I will describe how resistance to drugs emerges by a variety of mechanisms, not only through direct interference with drug binding but also destabilisation of protein interfaces and allostery. I will discuss the challenges of making new medicines against emerging resistance in cancer and tuberculosis.
AboutÂ Tom Blundell
Tom BlundellÂ is in Biochemistry at University of Cambridge, where he was previously Sir William Dunn Professor between 1996 and 2009. He has held positions in Universities of London, Sussex and Oxford. Tom researches on molecular, structural and computational biology of receptor activation, signal transduction and DNA repair, important in cancer, tuberculosis and familial diseases. He has published 560 research papers, including 30 in Nature. In 1999 he co-founded Astex Therapeutics, an oncology company that was sold in 2013 to Otsuka for $886 million. Tom has been a member of PM Thatcherâs Advisory Council, founding CEO BBSRC, Deputy Chair ICR and President, Science Council.
Key publications:1 .Â Â Sibanda BL, Chirgadze DY, Blundell TL. (2010)Â Crystal structure of DNA-ÂPKcs reveals a large open-Âring cradle comprised of HEAT repeats. Nature. 463: 118-Â21. 2.Â Â Worth CL, Gong S, Blundell TL. (2009)Â Structural and functional constraints in the evolution of protein families. Nat Rev Mol Cell Biol. 10: 709-20. 3.Â Â Murray CW, Blundell TL. (2010)Â Structural biology in fragment-Âbased drug design. Curr Opin Struct Biol. 20: 497â507
Giving OpportunitiesThe endowed lecture series wasÂ established by David's family, justÂ one of many waysÂ in which people have helped make a difference in advancing UC Davis's commitments to teaching, research, and public service.
- 2015Â Lecture:Â ProfessorÂ Stephen Quake, School of Engineering, Stanford University and Howard Hughes Medical Institute.Â Single Cell Genomics.
- 2014:Â ProfessorÂ Arup Chakraborty, Laboratory for Computational Immunology, Massachusetts Institute of Technology.Â How to Hit HIV Where It Hurts.
- 2013:Â ProfessorÂ Joanna Aizenberg, Harvard University, School of Engineering and Applied Science.Â Novel Biomimetic 'Spiny' Surfaces in Medical Applications.
- 2012:Â ProfessorÂ Cheryl Arrowsmith, Structure Genomic Consortium, Department of Medical Biophysics, University of Toronto.Â Structural and Chemical Biology of Epigenetic Regulators.
- 2011:Â ProfessorÂ John Kuriyan, Chancellor's Professor, Department of Molecular and Cell Biology and Department of Chemistry, University of California, Berkeley.Â Molecular Mechanisms in Signal Transduction by Tyrosine Kinases.
- 2010:Â ProfessorÂ Susan Lindquist, Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Broad Institute of MIT and Harvard Department of Biology, MIT.Â Protein Folding Driving the Evolution of Genomes.
- 2009:Â ProfessorÂ 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.Â Structural Neurology: Understanding, Treating and Preventing Neurodegenerative Diseases.
- 2008:Â ProfessorÂ Christopher Dobson, John Humphrey Plummer Professor of Chemical and Structural Biology, Master of St. Johns College, Cambridge University, United Kingdom.Â Life on the Edge: The Nature and Origins of Protein Misfolding Diseases.
- Invited guest speaker, Professor Rohit Pappu, Washington University,Â A Student's Remembrance of David Weaver.
- 2007:Â ProfessorÂ Martin Karplus, Laboratoire de Chimie Biophysique, ISIS, Universite Louis Pasteur and Department of Chemistry and Chemical Biology, Harvard University, 2013 Nobel Prize in Chemistry, Â How Proteins Work: Insights from Simulations.
- Opening remarks by Dirk Laukien, Ph.D., Senior Scientific Fellow, Bruker Optics,Â Unfolding David Weaver's Contributions at Bruker Optics.