Roger D. Kornberg

Roger David Kornberg (born April 24 1947(1947-04-24)) 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 molecular basis of eukaryotic transcription" which explains the process by which genetic information from DNA is copied to RNA.^[1][2] His father, Arthur Kornberg, who was also a professor at Stanford University, was awarded the Nobel Prize in Medicine in 1959.

He also holds an honorary doctorate from Umeå University in Sweden.

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Biography

Kornberg was born in St. Louis, Missouri to a Jewish family. He was the first of three children born to biochemists Arthur Kornberg and his wife, Sylvy (née Levy), who worked together.

Roger Kornberg earned his bachelor's degree from Harvard University in 1967 and his Ph.D. from Stanford in 1972. He conducted post-doctoral research at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom. He joined Harvard Medical School in 1976 as an assistant professor in the department of biological chemistry. Kornberg returned to Stanford in 1978 as a professor in the structural biology department. He served as department chair from 1984 until 1992. He serves as the Mrs. George A. Winzer Professor in Medicine at Stanford University School of Medicine.

Kornberg is also a visiting professor at the Hebrew University of Jerusalem, Israel, where he has taught and conducted research for four months every year since 1986.^[3][4]

Kornberg is a member of the United States National Academy of Sciences and the American Academy of Arts and Sciences.

Scientific Discoveries and Nobel Prize

All organisms are to some extent controlled by their genetic makeup. In order for the organism to make use of the information stored in the genes, a copy must first be made and transferred to the outer parts of the cells. The process by which the genes are copied is called transcription. Transcription makes an RNA copy of a region of the DNA that comprises the gene in question. The RNA is subsequently transported out of the nucleus, where it performs its function. Most of this so-called messenger RNA serves as instructions for protein production, in a process called translation. In most cases, proteins perform a cellular function specified by the gene. The enzyme responsible for the synthesis of protein-coding mRNA is termed RNA polymerase II. Kornberg has worked to understand this process in eukaryotes, a huge evolutionary group encompassing all organisms with well-defined nuclei, i.e., everything from yeast to humans. In contrast to bacterial RNA polymerases, eukaryotic RNA polymerases are alone incapable of gene transcription, and require a complex assembly of accessory proteins to accomplish this task in an accurate and efficient manner.

Roger Kornberg and his research group have made several fundamental discoveries concerning the mechanisms and regulation of eukaryotic transcription. 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" to reflect this protein packaging).^[5] 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.^[6] 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."^[7]

At the same 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.^[8][9] The structure of RNA polymerase obtained by Kornberg is the most complex protein structure solved to date. He has recently extended these studies to obtain structural images of RNA polymerase associated with accessory proteins.^[10]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."^[11]

In 1959, Roger Kornberg's father, Arthur Kornberg, received the Nobel Prize in Physiology or Medicine for studies of how genetic information is transferred from one DNA molecule to another in a process called DNA replication. Specifically, Arthur Kornberg isolated the first enzyme capable of synthesizing DNA, bacterial DNA polymerase I, which was then the first known enzyme to take its instructions from a template, thus ensuring the conservation of genetic information during cellular growth and division. Roger Kornberg's younger brother, Thomas Bill Kornberg, discovered DNA polymerases II and III in 1970 and is now a geneticist at the University of California, San Francisco. All three Kornbergs have thus worked to understand how genetic information is put to use in cells. Roger and Arthur Kornberg are the sixth father-son pair to win Nobel Prizes.

Awards

He has received the following awards:

• 1997: Harvey Prize from the Technion - Israel Institute of Technology
• 2002: ASBMB-Merck Award
• 2002: Pasarow Award in Cancer Research
• 2002: Le Grand Prix Charles-Leopold Mayer
• 2005: General Motors Cancer Research Foundation’s Alfred P. Sloan Jr. Prize^[12]
• 2006: Nobel Prize in Chemistry
• 2006: Louisa Gross Horwitz Prize from Columbia University

References