2006 Dickson Prize Winner
Roger D. Kornberg, PhD
Mrs. George A. Winzer Professor in Medicine
Professor of Structural Biology
Stanford University School of Medicine
2006 Dickson Prize in Medicine Lecture
“Chromatin and Transcription”
In the pivotal biological process called transcription, a cell's genes are selectively transcribed from double-stranded DNA into single-stranded RNA, thereby establishing a cell's genetic blueprint; determining whether it becomes a blood, nerve, liver, or other type of cell; and giving the human genome its voice, so to speak.
Central to this process is RNA polymerase, the enzyme that copies DNA into messenger RNA and that, in the words of Roger D. Kornberg, PhD, is “arguably the most important protein in biology” because “the structure provides the basis for understanding all gene activity in eukaryotic cells.”
The fundamental basis of gene regulation, including the control of transcription as the first step in the pathway of gene expression, constitutes the research focus of Kornberg, who is the Mrs. George A. Winzer Professor in Medicine and professor of structural biology at Stanford University School of Medicine. On the day before Kornberg presented the 2006 Dickson Prize Lecture, he was named the winner of the Nobel Prize in Chemistry for 2006.
“The work by the Kornberg laboratory stands out, most clearly, for its pioneering nature, for its breadth, for its uncompromising rigor, and for the essential nature of the structural innovations,” said Alexander Varshavsky, PhD, who nominated Kornberg for the 2006 Dickson Prize in Medicine. “The seminal contributions of Kornberg encompass the discovery of the nucleosome; the breakthrough development of a promoter-dependent transcription extract from yeast; the first resolution and reconstitution of an entire, regulated RNA polymerase II system, including the multiprotein Mediator complex; the pioneering development of methods for two-dimensional protein crystallography as well as their use for unprecedented structural dissection of the huge molecular complexes that mediate transcription in eukaryotes; and, finally, the extraordinary structure determination of the RNA polymersase II complex.”
Kornberg’s own assessment of his work is simply this: “You can’t understand a machine if you don’t know the place of all the pieces, and our discoveries have helped locate the parts of the machine that makes RNA.” Consequently, in unraveling the inner workings of RNA, his research team has isolated the proteins responsible for transcription and gene regulation, including those that form a mediator to regulate the process and assure that the right gene turns on at the right place and at the right time. Kornberg said, “Our work has accomplished two things—first, an understanding at the atomic level of how transcription occurs and, second, a description of how it is regulated.”
In the process, his research also helps elucidate how disease can result when transcription goes awry—how a gene can mutate and cause cancer, for instance—and offers the potential for unlocking new therapeutic approaches. As a result, Kornberg won the 2005 Alfred P. Sloan Jr. Prize, one of a trio of prestigious honors in the General Motors Cancer Research Awards Program. Among his other honors are the Pasarow Award in Cancer Research from the Pasarow Foundation, Le Grand Prix Charles-Léopold Mayer from the Académie des Sciences in France, the Welch Award in Chemistry from the Welch Foundation, and the Hoppe-Seyler Award from the German Society for Biochemistry and Molecular Biology. In addition, he shared the Merck Award from the American Society for Biochemistry and Molecular Biology and the Gairdner International Award from the Gairdner Foundation with Robert G. Roeder, PhD, winner of the 2001 Dickson Prize in Medicine.
Kornberg is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences. He holds honorary degrees from the University of Umea in Sweden and Hebrew University of Jerusalem in Israel.
A graduate of Harvard University with a BS in chemistry, Kornberg earned his PhD in chemistry from Stanford University in 1972. Following postdoctoral work at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, he stayed for a second fellowship and then became a member of the scientific staff. In 1976, he joined the Department of Biological Chemistry at Harvard Medical School. Two years later, Kornberg returned to Stanford as a professor of structural biology. He chaired the Department of Structural Biology there from 1984 to 1992, and in 2003 he became the first Winzer Professor in Medicine.
(Originally published Oct. 5, 2006)