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Vol.25, No. 15 Feb. 25, 2000

Chambon, Roeder and Tjian Receive Horwitz Prize

The Louisa Gross Horwitz Prize Ceremony on Feb. 3 in Low Rotunda honored Pierre Chambon, Robert Roeder and Robert Tjian for their pioneering work in understanding the transcription of genetic material into messenger RNA—one of the most fundamental and critical processes in the life of all cells.

The prestigious Horwitz prize has been given annually by Columbia since 1967 for outstanding research in biology or biochemistry. The prize carries a monetary award of $22,000.

Chambon is director of the Institut de Génétique et de Biologie Moléculaire et Cellulaire at the Université Louis Pasteur in Strasbourg, France. Roeder is head of the Laboratory of Biochemistry and Molecular Biology at Rockefeller University. Tjian is professor of biochemistry at UC-Berkeley and a Howard Hughes Medical Institute Investigator.

Their work has shed light on how genetic material is transcribed into messenger RNA, the proteins that act on the instructions of our genes. The difference between a blood cell and a muscle cell depends upon which parts of a cell's DNA are converted to mRNA, or expressed, and errors in the transcription process are a major cause of cancer and other diseases.

Chambon has studied the control of gene expression in eukaryotes, organisms with membrane-bound nuclei, for more than 40 years. Eukaryotic organisms range from single-celled animals to humans, and Chambon has discovered how molecules that promote gene transcription are organized in these organisms. He has also identified DNA sequences called enhancers that stimulate gene expression, and has characterized a large family of nuclear receptors, including steroid and retinoid receptors. These are structures within the cell nucleus that act as "switches" for certain types of gene expression when stimulated by a particular molecule.

Chambon's work has paved the way to molecular understanding of such fundamental processes as embryonic development and cell differentiation.

Roeder has spent his 30-year career studying the mechanism and regulation of gene expression during cell growth, differentiation and virus infection. This process is controlled largely at the level of transcription—making RNA copies of the DNA—and transcription initiation factors, which launch the transcription process, are a particular focus of his research. Roeder's early work led to the discovery of the general transcription machinery: distinct nuclear RNA polymerases (in 1969) and cognate general initiation factors (in 1980). He and his colleagues also identified the first gene-specific transcriptional activator (in 1980) and its corresponding gene (in 1984). He has also helped to describe how general transcription factors and gene-specific activator proteins interact, through the agency of other cofactors, to initiate gene expression. The function of gene- and cell-specific transcriptional activators and coactivators in normal cell growth and differentiation, and in pathogenesis, is a continuing focus of his research.

Tjian has been studying transcription regulation for more than 25 years. The DNA tumor virus SV40 was the initial focus of his research. This virus takes over the genetic machinery of the cells it infects in order to express its own genes. Tjian's work led to the first characterization of a eukaryotic regulatory protein, the SV40 tumor antigen, that binds to specific signals in DNA, and to the discovery that the activator AP1 consists of the products of two oncogenes. This discovery demonstrated directly that diseases such as cancer may be caused by defects in the control of transcription.

Tjian and his colleagues have characterized a large number of components of transcriptional machinery, especially those responsible for its activation and regulation.