May 8th: Weaver Lecture 2019, Professor Carol W. Greider

Overview

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.

The 2019 Lecture: Professor Carol W. Greider 'Telomeres and Telomerase: From Fundamental Mechanisms to Disease'

Date: Wednesday, May 8th 2019, 3pm, GBSF 1005.

Carol Grieder is a Professor of Molecular Biology and Genetics at Johns Hopkins University School of Medicine.

Telomeres are the structures at the end of chromosomes, made of repetitive DNA, that protect chromsomes ends. Every time a cell divides telomeres shorten by a small amount. This shortening is counter balanced by the enzyme telomerase, which adds telomere DNA repeats and elongates telomeres. Telomeres are thus not unique size but rather are maintained about an equilibrium length. If telomere length is not properly maintained, and they become too short and cause cell death. Problems with telomere length maintenance are associated with human disease including age-related degenerative disease and cancer. Failure to maintain telomeres in adult stem cells causes loss of tissue renewal that leads to inherited Short Telomere Syndromes in humans. These diseases include pulmonary fibrosis, immunodeficiency, bone marrow failure and liver disease. Conversely cancer cells increased telomere length maintenance to allow for continuous cell division. To understand the mechanisms of these diseases, the Greider lab is focused  establishing the molecular basis for the establishing the telomere length equilibrium.

About Carol W. Greider

Carol Greider, Ph.D. received her bachelor's degree from the University of California at Santa Barbara in 1983 and a Ph.D. in 1987 from the University of California at Berkeley. In 1984, working together with Dr. Elizabeth Blackburn, she discovered telomerase, an enzyme that maintains telomeres, or chromosome ends.  In 1988, Dr. Greider went to Cold Spring Harbor Laboratory where, as an independent Cold Spring Harbor Fellow, she cloned and characterized the RNA component of telomerase.  In 1990, Dr. Greider was appointed as an assistant investigator at Cold Spring Harbor Laboratory, followed later by appointment to Investigator in 1994. She expanded the focus of her telomere research to include the role of telomere length in cellular senescence, cell death and in cancer.  In 1997, Dr. Greider moved her laboratory to the Department of Molecular Biology and Genetics at The Johns Hopkins University School of Medicine.  In 2003 she was appointed as the Daniel Nathans Professor and Director of the Department of Molecular Biology and Genetics.  At Johns Hopkins University, Dr. Greider's group continued to study the biochemistry of telomerase and determined the secondary structure of the human telomerase RNA. In addition she characterized the loss of telomere function in mice, which allowed an understanding of short telomere syndromes in humans such as bone marrow failure, pulmonary fibrosis and other diseases. Dr. Greider shared the Nobel Prize in Physiology or Medicine in 2009 with Drs. Elizabeth Blackburn and Jack Szostak for their work on telomeres and telomerase. Dr. Greider currently directs a group of eight scientists studying both the role of short telomeres in age-related disease and cancer as well as the regulatory mechanism that maintain telomere length.

Key Publications

1. Greider, C.W., and Blackburn, E.H.  Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell (1985) 43: 405–413.
2. Harley, C.B., Futcher, A.B., and Greider, C.W.  Telomeres shorten during ageing of human fibroblasts. Nature (1990) 345: 458–460.
3. Autexier, C., and Greider, C.W.  Boundary elements of the Tetrahymena telomerase RNA template and alignment domains. Genes & Dev. (1995) 9: 2227-2239.
4. Hemann, M.T., and Greider, C.W.  Wild derived inbred mouse strains have short telomeres, Nucleic Acids Res. (2000) 28: 4474-4478.
5. Chen, J.-L., and Greider, C.W. Functional analysis of the pseudoknot structure in human telomerase RNA. Proc. Natl. Acad. Sci. U.S.A. (2005) 102: 8080-8085.
6. Vidal-Cardenas, S.L., and Greider, C.W.  Comparing effects of mTR and mTERT deletion on gene express and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase.  Nucleic Acids Res. (2010) 38: 60-71.
7. Kaizer, H., Connelly, C.J., Bettridge, K., Viggiani, C., and Greider, C.W. Regulation of Telomere Length Requires a Conserved N-Terminal Domain of Rif2 in Saccharomyces cerevisiae. Genetics (2015) 201:573-586.
8. Pike, A.M., Strong, MS, Ouyang, J.P., Connelly, C. J. Greider, C.W. TIN2 functions with TPP1/POT1 to stimulate telomerase processivity. (2018) BioRxiv:doi: https://doi.org/10.1101/435958

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.

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

• 2018: Professor Jody Puglisi, Structural Biology, Stanford University. The Delicate Dance of Translation. (video)
• 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.

 

Telomeres are the structures at the end of chromosomes, made of repetitive DNA, that protect chromsomes ends. Every time a cell divides telomeres shorten by a small amount. This shortening is counter balanced by the enzyme telomerase, which adds telomere DNA repeats and elongates telomeres. Telomeres are thus not unique size but rather are maintained about an equilibrium length. If telomere length is not properly maintained, and they become too short and cause cell death. Problems with telomere length maintenance are associated with human disease including age-related degenerative disease and cancer. Failure to maintain telomeres in adult stem cells causes loss of tissue renewal that leads to inherited Short Telomere Syndromes in humans. These diseases include pulmonary fibrosis, immunodeficiency, bone marrow failure and liver disease. Conversely cancer cells increased telomere length maintenance to allow for continuous cell division. To understand the mechanisms of these diseases, the Greider lab is focused  establishing the molecular basis for the establishing the telomere length equilibrium.

About Carol W. Greider

Carol Greider, Ph.D. received her bachelor's degree from the University of California at Santa Barbara in 1983 and a Ph.D. in 1987 from the University of California at Berkeley. In 1984, working together with Dr. Elizabeth Blackburn, she discovered telomerase, an enzyme that maintains telomeres, or chromosome ends.  In 1988, Dr. Greider went to Cold Spring Harbor Laboratory where, as an independent Cold Spring Harbor Fellow, she cloned and characterized the RNA component of telomerase.  In 1990, Dr. Greider was appointed as an assistant investigator at Cold Spring Harbor Laboratory, followed later by appointment to Investigator in 1994. She expanded the focus of her telomere research to include the role of telomere length in cellular senescence, cell death and in cancer.  In 1997, Dr. Greider moved her laboratory to the Department of Molecular Biology and Genetics at The Johns Hopkins University School of Medicine.  In 2003 she was appointed as the Daniel Nathans Professor and Director of the Department of Molecular Biology and Genetics.  At Johns Hopkins University, Dr. Greider's group continued to study the biochemistry of telomerase and determined the secondary structure of the human telomerase RNA. In addition she characterized the loss of telomere function in mice, which allowed an understanding of short telomere syndromes in humans such as bone marrow failure, pulmonary fibrosis and other diseases. Dr. Greider shared the Nobel Prize in Physiology or Medicine in 2009 with Drs. Elizabeth Blackburn and Jack Szostak for their work on telomeres and telomerase. Dr. Greider currently directs a group of eight scientists studying both the role of short telomeres in age-related disease and cancer as well as the regulatory mechanism that maintain telomere length.