Masayasu Nomura

Dr. Masaysu Nomura was a gifted biologist who contributed seminally to the development of modern molecular biology.  Born in 1927, Dr. Nomura grew up during the war years, and completed his BS and PhD at Tokyo University during the challenging post war years. He then came to the US as a postdoctoral fellow in the laboratories of pioneers of molecular biology S. Spiegelman at the University of Illinois, J. Watson at Harvard University, and S. Benzer at Purdue from 1957 to 1960. At that time, DNA was known to encode genes but the mechanism through which this information was used to express proteins, the building blocks of cellular material, was not. At this time, the focus of his research was on changes in RNA species which occurred upon T4 infection. Work in the Benzer laboratory, including that performed by Nomura, led to the paradigm-shifting insight that there was a one to one to one relationship between these genes, these RNA species and the proteins which they encode.

Masayasu returned to Japan briefly before being recruited back to the United States by the University of Wisconsin where he joined the faculty as an Associate Professor in Genetics 1963. In 1966 he was promoted to Professor and in 1970 he was named the Elvehjem Professor in Life Sciences of the Institute for Enzyme Research at the University of Wisconsin with joint appointments in the Departments of Genetics and Biochemistry.  In the early period of research at the University of Wisconsin, the Nomura lab established its preeminence in the emerging field of protein synthesis. A driving theme in his research was the relationship between growth control and control of this protein synthesis. Much of the focus of the laboratory was on the characterization of a poorly understood complex of proteins and RNAs called the ribosome, which attaches to mRNA and provides most of the catalytic functions required for protein synthesis. The Nomura lab dominated progress on the problems of the mechanism of protein synthesis initiation by ribosomes on mRNAs, the mechanism of regulation of synthesis of components of the ribosomes themselves, and ultimately the physical characterization of the ribosome itself and the contributions of its components to translation. A central experimental accomplishment and one of almost unimaginable complexity at that time was the assembly of a functional bacterial ribosome from its constituent tens of proteins and RNAs. These fundamental contributions to our understanding of one of the most basic of cellular processes were recognized with a number of awards and memberships in honorific societies. Recognition included election to the American Academy of Arts and Sciences, the National Academy of Sciences USA, the Royal Danish Academy of Sciences and Letters, and the Royal Netherlands Academy of Arts and Sciences.

In 1984, Dr. Nomura was recruited to the UCI campus by the School of Medicine and the Department of Biological Chemistry. In addition to increasing the prestige of UCI by contributing to its research activity, Nomura brought community recognition and commercial funds and growth to the campus. In 1986 he was the recipient of dual awards from the Hitachi Chemical Fund of $600,000 and $250,000 from Grace Bell.  These awards resulted in the establishment of the Grace Bell Chair of Biological Chemistry for the School of Medicine that continues to lend prestige to accomplished researchers. In addition, Nomura was responsible for the personal interactions which resulted in UCI School of Medicine being selected as the site of a 16.7 million dollar construction of the Hitachi Research facility and Plumwood Building. This facility houses Department of Biological Chemistry investigators on its first floor and its ownership will eventually revert completely to the UCI campus.

While Nomura’s interest in control of protein synthetic machinery continued, upon joining UCI, the emphasis of his laboratory shifted from studies of prokaryotic cells to eukaryotic cells. In particular, he chose to focus on the specialized polymerase (Pol I) in eukaryotic cells that synthesizes the RNA component of ribosomes. At the time he began those studies, only Pol I and minimal promoter features important for Pol I activity had been identified in mammalian cells.

Nomura and his team undertook to study Pol I expression of the genes for ribosomal RNA in the model yeast Saccharomyces.  They immediately capitalized on the sophisticated genetics then becoming available in Saccharomyces to craft a selection system with which the genes encoding proteins required for pol I transcription and the promoter sequences required for their activity could be identified in vivo. His group leveraged those findings to develop the first in vitro system for Pol I transcription of ribosomal RNA and used it to further define the essential functions of these factors and sequences. Surprisingly they found among these subunits a histone protein and a subunit TBP which was subsequently shown to be required for transcription by any of the three eukaryotic polymerases. In some of their most elegant work, they studied the physical interactions and localization of the ribosomal RNA genes themselves. These genes occur in eukaryotes as highly-repeated sequences localized in specialized nucleolar structures. Nomura and collaborators expert in electron microscopy showed effects of ribosomal RNA gene position and transcribing (Pol I vs artificially mediated Pol II expression), rather than transcriptional activity per se, influence nuclear position of the nucleolus. His laboratory studied the mechanism critical for downregulation of recombination among these repeated gene sequences and finally showed that Pol I itself was dispensable if ribosomal RNA was expressed synthetically by another of the three yeast polymerases, Pol II.

Nomura was generous with his biological reagents so that other investigators later were able to exploit his constructs and mutants in their studies of Pol I transcription and further amplify his contributions. Yeast continues to represent the eukaryotic system best understood for this polymerase which is critical to production of protein synthetic machinery.

During the time that Nomura was at UCI he received international recognition for his contributions to our understanding of fundamental biological processes. He was elected an honorary member of the Japanese Biochemcial Society, received an honorary doctorate from Purdue University, and was inducted into Japan Society for Bioscience Biotechnology and Agrochemicals, and American Academy of Microbiology. He received the UCI Senate Distinguished Senior Faculty Award for Research; School of Medicine Athalie Clarke Research Award and Abbott ASM Lifetime Achievement Award.

Throughout Nomura’s career until the time he passed away, he was funded by the National Institutes of Health and additionally by other foundations and agencies. Nomura was a powerful intellectual presence with a driving interest in biological mechanisms of growth regulation and high standards of scientific rigor. His dedication is perpetuated now by trainees and colleagues. During his career, he trained 17 Ph.D. students and 48 postdoctoral fellows. In addition to cultivating his own laboratory, he hosted numerous visiting scientists who also enriched the campus research environment. Within the basic science departments, Nomura was known to be a tough, but engaged mentor of junior scientists at all stages.  Among his laboratory trainees are faculty members at the University of Illinois, the University of California, San Francisco, State University of New York, Albany, University of Rochester, Emory, University of Wisconsin, University of Pittsburgh, and University of Alabama.

For further readings about Dr. Nomura’s prolific scientific life please see: Journey of a Molecular Biologist in Annual Review of Biochemistry Vol. 80:16-40, 2011. https://www.annualreviews.org/doi/abs/10.1146/annurev-biochem-082808-091843

Suzanne Sandmeyer, Professor
Biological Chemistry, UC Irvine