Dr. Roger David Kornberg (born 1947)

Roger David Kornberg (born April 24,^[4] 1947) is an American biochemist and professor of structural biology at Stanford University School of Medicine. Kornberg was awarded the Nobel Prize in Chemistry in 2006 for his studies of the process by which genetic information from DNA is copied to RNA, "the molecular basis of eukaryotic transcription."^{[5][6][7][8][9][10]}

Contents

Education and early life[edit]

Kornberg was born in St. Louis, Missouri, the eldest son of biochemist Arthur Kornberg, who won the Nobel Prize, and Sylvy Ruth (Levy) who was also a biochemist. He earned his bachelor's degree in chemistry from Harvard University in 1967 and his Ph.D. in chemical physics from Stanford in 1972 supervised by Harden M. McConnell.^[3]

Career[edit]

Kornberg became a postdoctoral research fellow at the Laboratory of Molecular Biology in Cambridge, England and then an Assistant Professor of Biological Chemistry at Harvard Medical School in 1976, before moving to his present position as Professor of Structural Biology at Stanford Medical School in 1978.^[11] Since 2004, Kornberg has been the editor of the Annual Review of Biochemistry.^[12]

Research[edit]

Kornberg in 2006

Roger D. Kornberg (third from left) with Andrew Fire, George Smoot, Dick Cheney, Craig Mello and John C. Mather

All organisms have genes, which are coded by DNA, which is copied to RNA, which creates proteins, which are sequences of amino acids. DNA resides in the nucleus. When a cell expresses a gene, it copies (transcribes) that gene's DNA sequence onto a messenger RNA (mRNA) sequence. mRNA is transported out of the nucleus to ribosomes. The ribosomes read the mRNA and translate the code into the right amino acid sequence to make that gene's protein.^[13]

The DNA is transcribed to mRNA by an enzyme, RNA polymerase II, with the help of many other proteins. Using yeast, Kornberg identified the role of RNA polymerase II and other proteins in transcribing DNA, and he created three-dimensional images of the protein cluster using X-ray crystallography. Polymerase II is used by all organisms with nuclei, including humans, to transcribe DNA.^[14]

Kornberg and his research group have made several fundamental discoveries concerning the mechanisms and regulation of eukaryotic transcription. While a graduate student working with Harden McConnell at Stanford in the late 1960s, he discovered the "flip-flop" and lateral diffusion of phospholipids in bilayer membranes. While a postdoctoral fellow working with Aaron Klug and Francis Crick at the MRC in the 1970s, Kornberg discovered the nucleosome as the basic protein complex packaging chromosomal DNA in the nucleus of eukaryotic cells (chromosomal DNA is often termed "Chromatin" when it is bound to proteins in this manner, reflecting Walther Flemming's discovery that certain structures within the cell nucleus would absorb dyes and become visible under a microscope).^[15] Within the nucleosome, Kornberg found that roughly 200 bp of DNA are wrapped around an octamer of histone proteins. With Yahli Lorch, Kornberg showed that a nucleosome on a promoter prevents the initiation of transcription, leading to the recognition of a functional role for the nucleosome, which serves as a general gene repressor.^[16]

Kornberg's research group at Stanford later succeeded in the development of a faithful transcription system from baker's yeast, a simple unicellular eukaryote, which they then used to isolate in a purified form all of the several dozen proteins required for the transcription process. Through the work of Kornberg and others, it has become clear that these protein components are remarkably conserved across the full spectrum of eukaryotes, from yeast to human cells.^[17]

Using this system, Kornberg made the major discovery that transmission of gene regulatory signals to the RNA polymerase machinery is accomplished by an additional protein complex that they dubbed Mediator.^[18] As noted by the Nobel Prize committee, "the great complexity of eukaryotic organisms is actually enabled by the fine interplay between tissue-specific substances, enhancers in the DNA and Mediator. The discovery of Mediator is therefore a true milestone in the understanding of the transcription process."^[19]

At the same time as Kornberg was pursuing these biochemical studies of the transcription process, he devoted two decades to the development of methods to visualize the atomic structure of RNA polymerase and its associated protein components. Initially, Kornberg took advantage of expertise with lipid membranes gained from his graduate studies to devise a technique for the formation of two-dimensional protein crystals on lipid bilayers. These 2D crystals could then be analyzed using electron microscopy to derive low-resolution images of the protein's structure. Eventually, Kornberg was able to use X-ray crystallography to solve the 3-dimensional structure of RNA polymerase at atomic resolution.^[20][21] He has recently extended these studies to obtain structural images of RNA polymerase associated with accessory proteins.^[22] Through these studies, Kornberg has created an actual picture of how transcription works at a molecular level. According to the Nobel Prize committee, "the truly revolutionary aspect of the picture Kornberg has created is that it captures the process of transcription in full flow. What we see is an RNA-strand being constructed, and hence the exact positions of the DNA, polymerase and RNA during this process."^[23]

Lipids membrane[edit]

As a graduate student at Stanford University, Kornberg's studied the rotation of phospholipids and defined for the first time the dynamics of lipids in the membrane.^[24] Kornberg called the movement of lipid from one leaflet to the other flip-flop because he had studied only a few years before electronic circuit elements called flip-flops. The term gave rise to the naming of proteins called flippases and floppases.^[25]

Industrial collaborations[edit]

Kornberg has served on the Scientific Advisory Boards of the following companies: Cocrystal Discovery, Inc (Chairman), ChromaDex Corporation (Chairman), StemRad, Ltd, Oplon Ltd (Chairman), and Pacific Biosciences. Kornberg has also been a director for the following companies: OphthaliX Inc., Protalix BioTherapeutics, Can-Fite BioPharma, Ltd, Simploud and Teva Pharmaceutical Industries, Ltd.

Awards and honors[edit]

Kornberg has received the following awards:

1981: Eli Lilly Award in Biological Chemistry
1982: Passano Award from the Passano Foundation
1990: Ciba-Drew Award
1997: Harvey Prize from the Technion – Israel Institute of Technology
2000: Gairdner Foundation International Award
2001: Hoppe-Seyler Award, Society for Biochemistry and Molecular Biology, Germany^[26]
2001: Welch Award in Chemistry
2002: ASBMB-Merck Award^[^{citation needed}^]
2002: Pasarow Award in Cancer Research
2002: Grand Prix Charles-Leopold Mayer
2003: Elected to EMBO Membership ^[2]
2003: Massry Prize from the Keck School of Medicine, University of Southern California
2005: General Motors Cancer Research Foundation’s Alfred P. Sloan, Jr. Prize^[27]
2006: Dickson Prize from University of Pittsburgh
2006: Nobel Prize in Chemistry
2006: Louisa Gross Horwitz Prize from Columbia University^[28]
2008: American Philosophical Society Membership
2009: Elected a Foreign Member of the Royal Society (ForMemRS)^[1]

References[edit]

^
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^a ^b Anon (2009). "Certificate of Election EC/2009/48: Roger D. Kornberg". London: Royal Society. Archived from the original on 2015-08-06.
^
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^a ^b "Roger D. Kornberg". people.embo.org.
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^a ^b Kornberg, Roger David (1972). The Diffusion of Phospholipids in Membranes (PhD thesis). Stanford University. OCLC 38611465. ProQuest 302673759.
^ "The Nobel Prize in Chemistry 2006". NobelPrize.org. Retrieved 2020-06-01.
^ "Roger Kornberg wins the 2006 Nobel Prize in Chemistry". Stanford University School of Medicine.
^ "Press release: The Nobel Prize in Chemistry 2006". Royal Swedish Academy of Sciences.
^ N, Kresge; Al., Et (2009). "The Decade-long Pursuit of a Reconstituted Yeast Transcription System: the Work of Roger D. Kornberg". J Biol Chem. 284 (43): e18-20. doi:10.1016/S0021-9258(20)38209-0. PMC 2785628. PMID 19847957.
^ BBC News report of Kornberg's Nobel Prize win
^ Kornberg Nobel Prize lecture
^ The Nobel Foundation 2006 prizes in Chemistry
^ Vasmatkar, Pashupat; Kamaljit, Kaur (2019). Miracles in Biochemistry: The contribution of the Nobel laureates to the field of Biochemistry. India: Educreation Publishing. p. 99. ISBN 978-9388910743. Retrieved 8 September 2021.
^ Richardson, Charles C. (2 June 2015). "It Seems Like Only Yesterday". Annual Review of Biochemistry. 84 (1): 1–34. doi:10.1146/annurev-biochem-060614-033850. PMID 26034887.
^ Davis, Alison (1990). "Chapter 2: Cells 101 Business basics". In Pines, Maya (ed.). Inside the cell (Rev. July 1990 ed.). [Bethesda, Md.?]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of General Medical Sciences. pp. 22–26. ISBN 9780160243813. Retrieved 8 September 2021.
^ Hirota, Noboru (2016). A history of modern chemistry. Kyoto, Japan: Kyoto University Press, Trans Pacific Press. pp. 625–626. ISBN 9781920901141. Retrieved 8 September 2021.
^ Kornberg, R. D. (1974). "Chromatin Structure: A Repeating Unit of Histones and DNA". Science. 184 (4139): 868–871. Bibcode:1974Sci...184..868K. doi:10.1126/science.184.4139.868. ISSN 0036-8075. PMID 4825889.
^ Lorch, Yahli; LaPointe, Janice W.; Kornberg, Roger D. (1987). "Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones". Cell. 49 (7): 203–210. doi:10.1016/0092-8674(87)90561-7. PMID 3568125. S2CID 21270171.
^ Capa, Nossa (2001). "Our Journal Cover". Jornal Brasileiro de Patologia e Medicina Laboratorial. 37 (4): 231. doi:10.1590/S1676-24442001000400001. Retrieved 8 September 2021.
^ Kelleher, Raymond J.; Flanagan, Peter M.; Kornberg, Roger D. (1990). "A novel mediator between activator proteins and the RNA polymerase II transcription apparatus". Cell. 61 (7): 1209–1215. doi:10.1016/0092-8674(90)90685-8. ISSN 0092-8674. PMID 2163759. S2CID 4971987.
^ "The Nobel Prize in Chemistry 2006". NobelPrize.org. Retrieved 2020-06-01.
^ Cramer, P. (2001). "Structural Basis of Transcription: RNA Polymerase II at 2.8 Angstrom Resolution" (PDF). Science. 292 (5523): 1863–1876. doi:10.1126/science.1059493. hdl:11858/00-001M-0000-0015-8729-F. ISSN 0036-8075. PMID 11313498. S2CID 4993438.
^ Gnatt, A. L. (2001). "Structural Basis of Transcription: An RNA Polymerase II Elongation Complex at 3.3 A Resolution". Science. 292 (5523): 1876–1882. doi:10.1126/science.1059495. hdl:11858/00-001M-0000-0015-8723-C. ISSN 0036-8075. PMID 11313499. S2CID 12379905.
^ Bushnell, D. A. (2004). "Structural Basis of Transcription: An RNA Polymerase II-TFIIB Cocrystal at 4.5 Angstroms". Science. 303 (5660): 983–988. Bibcode:2004Sci...303..983B. doi:10.1126/science.1090838. ISSN 0036-8075. PMID 14963322. S2CID 36598301.
^ A family story about life 2006
^ Kornberg, RD; McConnell, HM (October 1971). "Lateral diffusion of phospholipids in a vesicle membrane". Proceedings of the National Academy of Sciences of the United States of America. 68 (10): 2564–8. Bibcode:1971PNAS...68.2564K. doi:10.1073/pnas.68.10.2564. PMC 389469. PMID 4332815.
^ Epand, Richard M.; Ruysschaert, Jean-Marie (September 25, 2017). The biophysics of cell membranes : biological consequences. Singapore: Springer. pp. 33–34. ISBN 9789811062438. Retrieved 8 September 2021.
^ Hartl, Franz-Ulrich (2001). "Roger D. Kornberg Felix Hoppe-Seyler Lecturer 2001". Biological Chemistry. 382 (8): 1101–2. doi:10.1515/BC.2001.139. ISSN 1431-6730. PMID 11592389. S2CID 41857405.
^ "The 2005 Alfred P. Sloan, Jr. Laureate". Archived from the original on 2006-10-19. Retrieved 2006-10-04.
^ The Official Site of Louisa Gross Horwitz Prize

External links[edit]

Scholia has an author profile for Roger D. Kornberg.

Roger D. Kornberg on Nobelprize.org

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