American wins chemistry Nobel for RNA transcription

Roger Kornberg, PhD, professor of structural biology at the Stanford University School of Medicine, today was awarded the 2006 Nobel Prize in Chemistry for his work in understanding how DNA is converted into RNA, a process known as transcription.

In 2001 he published the first molecular snapshot of the protein machinery responsible — RNA polymerase — in action. The finding helped explain how cells express all the information in the human genome.

“I’m simply stunned, there’s no other words,” said Kornberg this morning after the 2:30 a.m. call. “It’s such astonishing news.”

Kornberg is the School of Medicine’s second Nobel Prize winner this week. On Monday, Andrew Fire, PhD, professor of pathology and of genetics, won the 2006 Nobel Prize in Physiology or Medicine.

Kornberg’s research, and latest award, is a family affair: his father Arthur Kornberg was awarded the Nobel Prize in Physiology or Medicine in 1959 for studies of how genetic information is transferred from one DNA molecule to another. The Kornbergs are the sixth father-son team to win Nobel Prizes.

“I have felt for some time that he richly deserved it,” said the elder Kornberg, PhD, the Emma Pfeiffer Merner Professor of Biochemistry, Emeritus, at the School of Medicine. “His work has been awesome.”

“Roger Kornberg is one of our nation’s treasured scientists,” said Philip Pizzo, MD, dean of the School of Medicine. “He has dedicated his life and career to using the powerful tools of structural biology to elucidate the molecular mechanism of transcription. His remarkable studies have been acclaimed for the elegance and technical sophistication as well as the unique insights they have yielded. His work has deepened our understanding of the ‘message of life’ and how it contributes to both normal and abnormal human development, health and disease.”

Transcription of the 30,000 or so genes determines whether a cell becomes a neuron or a liver cell or a bone cell. Kornberg, the Mrs. George A. Winzer Professor in Medicine, has been studying the RNA and RNA polymerase for more than 30 years. The picture of RNA polymerase bound to both DNA and newly formed RNA provided a window into a process that had been only hinted at. It was a thing of beauty for biologists around the world.

“We were astonished by the intricacy and complexity of the complex, elegance of the architecture, and the way that such an extraordinary machine evolved to accomplish these important purpose,” said Kornberg. “RNA polymerase gives a voice to genetic information that, on its own, is silent.”

In a 2001 interview with the Houston Chronicle, Kornberg noted that aberrations in gene expression and transcription underlie many cellular events that lead to cancer. The broadest implication of his work, he said, is that “if we fully comprehend the regulation and expression of genes, then we can intervene.”

Kornberg’s studies have provided an understanding at the atomic level of how the ubiquitous process of transcription occurs and also how it is controlled. His work in determining the arrangement of the 30,000 atoms in the RNA polymerase also helps explain how the process sometimes goes awry, leading to birth defects, cancer and other diseases.

“Roger has succeeded at solving one of the largest and most central structures in molecular biology,” Michael Levitt, PhD, professor and prior chair of structural biology, told Medical Center Report in 2001 after Kornberg received the prestigious Welch Award in Chemistry. “Five years ago, no one in the field believed he had a chance of success.”

Prior to beginning his work studying the molecular mechanism of transcription, Kornberg discovered the nucleosome, the basic unit from which all chromosomes are made. In 1974, as a junior scientist at Cambridge University, he proposed that the massive amounts of DNA contained in every cell could be compactly stored by wrapping it in its condensed form—the chromosome—around eight histone protein “spools” to form nucleosome “beads.” Kornberg and his wife and collaborator Yahli Lorch, PhD, associate professor of structural biology at Stanford, were instrumental in identifying the nucleosome as fundamental to transcription. Since then, it has been recognized that disruptions involving the nucleosome underlie many cancers and other diseases.

Born in 1947, Kornberg was the first of three children born to Arthur Kornberg and his wife, Sylvy, who was also a biochemist working with Arthur.

At 3:55 a.m today, a few minutes after hearing about the award, Arthur Kornberg summed up how he felt about his son’s award: “Excited,” he said. “I am excited.”

The senior Kornberg said his son’s winning did not come entirely out of the blue and that he had mentioned the chemistry prize yesterday in a conversation with his son, who had just returned from a trip to Jerusalem. “I talked to him at length and couldn’t help but discuss this possibility — I know he’s been shortlisted in previous years,” said the elder Kornberg. “He dismissed it, saying it was a possibility but he didn’t expect it, but that’s the way it goes.”

Arthur Kornberg said he had not imagined decades ago, when his son first began his career as a biochemist, that there would be a second Nobel laureate in the family. “Of course not,” he remarked. “But nature is so broad, profound and mysterious — one doesn’t know where it leads. And I would say among the people I know — and I have trained many hundreds — he has the clearest vision, sense of purpose and direction.

“I’m a biochemist and he’s a biochemist but beyond that he’s a crystallographer, a structural chemist and a geneticist. He’s done all of those and maintained several groups under those categories and has had some outstanding students. The work has gone exceedingly well.”

Pizzo paid tribute to the contributions of both father and son to Stanford. “Arthur Kornberg played a major role in transforming the Stanford University School of Medicine to a research-intensive powerhouse,” Pizzo said. “He was clearly productive in both his professional life and his private life—since he is the father of remarkably talented children, including Roger, who has sustained a legacy of brilliance and commitment to science and the deepening of our understanding of human life.”

Roger Kornberg received his undergraduate degree in chemistry from Harvard in 1967 and his doctorate in chemistry from Stanford in 1972, studying the motion of lipids in cell membranes. He was a postdoctoral fellow and member of the scientific staff at the Laboratory of Molecular Biology in Cambridge, U.K., from 1972 to 1975. 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.

Kornberg is an elected member of the National Academy of Sciences and of the American Academy of Arts and Sciences, and an honorary member of the Japanese Biochemical Society. He is editor of the Annual Reviews of Biochemistry. He has written more than 180 peer-reviewed journal articles.

His previous honors and awards include the Eli Lilly Award (1981), the Passano Award (1982), the Harvey Prize (1997), the Gairdner International Award (shared in 2000 with Robert Roeder), the Welch Award (2001) and the Grand Prix of the French Academy of Sciences (2002).

“I’m looking forward to being in Stockholm, where we have many friends,” said Arthur Kornberg, remembering his own award 47 years ago. “They put on a great party.”

From Stanford University


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