Roger D. Kornberg
Encyclopedia
Roger David Kornberg 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
."
, Missouri
. He earned his bachelor's degree
in chemistry
from Harvard University
in 1967 and his Ph.D.
in chemical physics
from Stanford in 1972. He became a postdoctoral 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. His closest collaborator has been his wife, Professor Yahli Lorch.
s, which are sequences of amino acid
s. 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 ribosome
s. The ribosomes read the mRNA and translate
the code into the right amino acid sequence to make that gene's protein.
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.
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). Within the nucleosome, Kornberg found that roughly 200 bp of DNA are wrapped around an octamer of histone proteins.
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.
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
. 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."
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. He has recently extended these studies to obtain structural images of RNA polymerase associated with accessory proteins. 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."
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
biochemist
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
and professor
Professor
A professor is a scholarly teacher; the precise meaning of the term varies by country. Literally, professor derives from Latin as a "person who professes" being usually an expert in arts or sciences; a teacher of high rank...
of structural biology
Structural biology
Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations in their structures affect their function...
at Stanford University
Stanford University
The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
School of Medicine.
Kornberg was awarded the Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
in 2006 for his studies of the process by which genetic information from DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
is copied to RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
, "the molecular basis of eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
."
Biography
Kornberg was born in St. LouisSt. Louis, Missouri
St. Louis is an independent city on the eastern border of Missouri, United States. With a population of 319,294, it was the 58th-largest U.S. city at the 2010 U.S. Census. The Greater St...
, Missouri
Missouri
Missouri is a US state located in the Midwestern United States, bordered by Iowa, Illinois, Kentucky, Tennessee, Arkansas, Oklahoma, Kansas and Nebraska. With a 2010 population of 5,988,927, Missouri is the 18th most populous state in the nation and the fifth most populous in the Midwest. It...
. He earned his bachelor's degree
Bachelor's degree
A bachelor's degree is usually an academic degree awarded for an undergraduate course or major that generally lasts for three or four years, but can range anywhere from two to six years depending on the region of the world...
in chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
from Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
in 1967 and his Ph.D.
Ph.D.
A Ph.D. is a Doctor of Philosophy, an academic degree.Ph.D. may also refer to:* Ph.D. , a 1980s British group*Piled Higher and Deeper, a web comic strip*PhD: Phantasy Degree, a Korean comic series* PhD Docbook renderer, an XML renderer...
in chemical physics
Chemical physics
Chemical physics is a subdiscipline of chemistry and physics that investigates physicochemical phenomena using techniques from atomic and molecular physics and condensed matter physics; it is the branch of physics that studies chemical processes from the point of view of physics...
from Stanford in 1972. He became a postdoctoral 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. His closest collaborator has been his wife, Professor Yahli Lorch.
Scientific discoveries and Nobel Prize
All organisms are controlled by their genes, which are coded by DNA, which is copied to RNA, which creates proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, which are sequences of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s. DNA resides in the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
. When a cell expresses a gene, it copies (transcribes
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
) that gene's DNA sequence onto a messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
(mRNA) sequence. mRNA is transported out of the nucleus to ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
s. The ribosomes read the mRNA and translate
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
the code into the right amino acid sequence to make that gene's protein.
The DNA is transcribed to mRNA by an enzyme, RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
, with the help of many other proteins. Using yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
, 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
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
. Polymerase II is used by all organisms with nuclei, including humans, to transcribe DNA.
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
Aaron Klug
Sir Aaron Klug, OM, PRS is a Lithuanian-born British chemist and biophysicist, and winner of the 1982 Nobel Prize in Chemistry for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes.-Biography:Klug was...
and Francis Crick
Francis Crick
Francis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...
at the MRC in the 1970s, Kornberg discovered the nucleosome
Nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....
as the basic protein complex packaging chromosomal DNA in the nucleus of eukaryotic cells (chromosomal DNA is often termed "Chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
" when it is bound to proteins in this manner, reflecting Walther Flemming
Walther Flemming
Walther Flemming was a German biologist and a founder of cytogenetics.He was born in Sachsenberg near Schwerin as the fifth child and only son of the psychiatrist Carl Friedrich Flemming and his second wife, Auguste Winter...
's discovery that certain structures within the cell nucleus would absorb dyes and become visible under a microscope). Within the nucleosome, Kornberg found that roughly 200 bp of DNA are wrapped around an octamer of histone proteins.
Kornberg's research group at Stanford later succeeded in the development of a faithful transcription system from baker's yeast
Baker's yeast
Baker's yeast is the common name for the strains of yeast commonly used as a leavening agent in baking bread and bakery products, where it converts the fermentable sugars present in the dough into carbon dioxide and ethanol...
, 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.
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
Mediator (coactivator)
Mediator is a multiprotein complex that functions as a transcriptional coactivator. It was discovered by Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry...
. 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."
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
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
to solve the 3-dimensional structure
Protein structure
Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...
of RNA polymerase at atomic resolution. He has recently extended these studies to obtain structural images of RNA polymerase associated with accessory proteins. 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."
Awards
He has received the following awards:- 1981: Eli Lilly Award
- 1982: Passano Award, Passano FoundationPassano FoundationThe Passano Foundation, established in 1945, provides an annual award of $ 100 000 to an American research scientist whose work is thought to have immediate practical benefits. Many Passano laureates have subsequently won the Nobel Prize....
- 1990: Ciba-Drew AwardCiba-Drew AwardThe Ciba-Drew Award for Biomedical Research is an award jointly presented by Ciba-Geigy and Drew University.-Winners:*1995: Joseph Schlessinger and Arnold J. Levine*1992: Stuart L. Schreiber*1990: Roger David Kornberg*1985: Jean-Pierre Changeux...
- 1997: Harvey PrizeHarvey PrizeThe Harvey Prize is awarded by the Technion in Haifa, Israel. It is awarded in different disciplines of Science, Technology, Human Health, and Contributions to Peace in the Middle East. Two awards - each of $75,000 - are given away annually...
from the Technion – Israel Institute of Technology - 2000: Gairdner Foundation International AwardGairdner Foundation International AwardThe Gairdner Foundation International Award is given annually at a special dinner to three to six people for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a precursor to winning the Nobel Prize in Medicine; as of 2007, 69 Nobel...
- 2001: Hope-Seyler Award, Society for Biochemistry and Molecular Biology, Germany
- 2001: Welch Award in Chemistry
- 2002: ASBMB-Merck Award
- 2002: Pasarow Award in Cancer Research
- 2002: Gran Prix Charles-Leopold MayerGran Prix Charles-Leopold MayerThe Grand Prix Charles-Léopold Mayer is awarded annually by the Académie des Sciences de l'Institut de France to researchers who have performed outstanding work in the biological sciences; especially in the areas of cell or molecular biology...
- 2003: Massry Prize
- 2005: General MotorsGeneral MotorsGeneral Motors Company , commonly known as GM, formerly incorporated as General Motors Corporation, is an American multinational automotive corporation headquartered in Detroit, Michigan and the world's second-largest automaker in 2010...
Cancer Research Foundation’s Alfred P. SloanAlfred P. SloanAlfred Pritchard Sloan, Jr. was an American business executive in the automotive industry. He was a long-time president, chairman, and CEO of General Motors Corporation...
Jr. Prize - 2006: Dickson PrizeDickson PrizeThe Dickson Prize in Medicine and the Dickson Prize in Science were both established in 1969 by Joseph Z. Dickson and Agnes Fischer Dickson...
from University of PittsburghUniversity of PittsburghThe University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of... - 2006: Nobel Prize in ChemistryNobel Prize in ChemistryThe Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
- 2006: Louisa Gross Horwitz PrizeLouisa Gross Horwitz PrizeLouisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers that have made an outstanding contribution in basic research in the fields of biology or biochemistry....
from Columbia UniversityColumbia UniversityColumbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
External links
- Roger Kornberg Laboratory
- Biography and Bibliographic Resources, from the Office of Scientific and Technical InformationOffice of Scientific and Technical InformationThe Office of Scientific and Technical Information is a component of the Office of Science within the U.S. Department of Energy...
, United States Department of EnergyUnited States Department of EnergyThe United States Department of Energy is a Cabinet-level department of the United States government concerned with the United States' policies regarding energy and safety in handling nuclear material... - Kornberg Nobel Prize lecture
- List of Kornberg's publications
- The Nobel Foundation home page
- Press release from The Royal Swedish Academy of Sciences
- A brief biography of his life
- Further biographical details
- BBC News report of his Nobel Prize win
- The Official Site of Louisa Gross Horwitz Prize