Shigetada Nakanishi receives $500,000 Gruber Neuroscience Prize

4 November, 2007
Gruber Prizes, Media releases


Shigetada Nakanishi receives $500,000 Gruber Neuroscience Prize

for discoveries about the molecular processes that drive our nervous system.

Two early career researchers also recognized.

November 4, 2007, San Diego, California – Over the last forty years, Shigetada Nakanishi has unraveled many of the molecular secrets that underpin the function of the human nervous system. His work has created new tools for researchers, and new drug targets for pharmacologists.

Today at 2.30 pm he will receive the Gruber Neuroscience Prize at the Society for Neuroscience conference in San Diego. In the 2007 Gruber Lecture he will address the fundamental question of how synaptic transmission is regulated and integrated in the neural network.

A full understanding of the workings of the human brain is still decades or more away. But Shigetada Nakanishi’s work is bringing it closer. He is an unusual researcher who has both created sophisticated tools to help us investigate the brain, and used these tools to make remarkable discoveries about the molecular processes used throughout the nervous system: our senses, movement control, cognition, learning, memory and much more.

Nakanishi will be joined on stage by two early career neuroscientists who will each receive the Gruber International Research Award in Neuroscience, a $US50,000 scholarship.

–  Hanover Medical School researcher Hubert Lim is developing a new kind of “bionic ear” – a device that will restore hearing by bypassing the ear and directly stimulating an area which processes auditory input deep in the brain.

–  Yulia Lerner is trying to determine how our brains make sense of the complicated world our eyes behold. The Azerbaijan-born scientist – currently based at New York University – is using functional MRI to explore the involvement of different brain regions in this process.

“Shigetada Nakanishi is laying the foundations for us to understand how our brains work – from the molecular level through to the complex interactions between networks of neurons,” says Peter Gruber, Chairman of the Peter and Patricia Gruber Foundation.

The Neuroscience Prize honors leading scientists for distinguished contributions in the fields of the brain, spinal cord, and peripheral nervous system. The Foundation’s other international prizes are in Cosmology, Genetics, Justice, and Women’s Rights.

Nominations for the 2008 prizes are now open and close on December 31, 2007.

  • Profiles, photos, background information and nomination details for 2008 are available online at www.gruberprizes.org


Background: 2007 Neuroscience Prize

The official citation reads:

“The Peter and Patricia Gruber Foundation proudly presents the 2007 Neuroscience Prize to Shigetada Nakanishi who developed tools that enabled him and others to probe fundamental molecular mechanisms of nervous system function.  By expressing genes in frog oocytes, he discovered new genes of the nervous system and identified novel membrane receptors.  Some of these receptors respond to peptide hormones and others to glutamate, the major excitatory chemical signal of the brain.  These receptors are critical for many vital processes of the nervous system, including learning, memory and vision.”

More recently, he has devised and applied elegant techniques to understand in detail how receptors on neuron membranes act at critical stages in the operation of synaptic circuits.   His work integrates multiple levels of neuroscience, from molecules to complex neuronal networks.

Past Laureates of the Gruber Neuroscience Prize

·    2006: Masao Ito and Roger Nicoll, for work on the molecular and cellular bases of memory and learning

·    2005: Masakazu Konishi and Eric Knudsen, for work on the neural basis of sound localization

·    2004: Seymour Benzer, for applying the tools of molecular biology and genetics to the fruit fly, drosophila, and linking individual genes to their behavioral phenotypes

2007 Gruber Neuroscience Prize Selection Advisory Board Members

·    Carol A. Barnes, PhD, University of Arizona

·    Colin Blakemore, Professor, Medical Research Council

·    Linda S. Buck, PhD, Fred Hutchinson Cancer Research Center

·    Sten Grillner, Professor, Karolinska Institute

·    H. Robert Horvitz, Professor, Massachusetts Institute of Technology

·    Donald Price, Professor, Johns Hopkins University School of Medicine

·    Richard W. Tsien, Professor, Stanford University School of Medicine

The Gruber Prize Program honors contemporary individuals in the fields of Cosmology, Genetics, Neuroscience, Justice and Women’s Rights, whose groundbreaking work provides new models that inspire and enable fundamental shifts in knowledge and culture. The Selection Advisory Boards choose individuals whose contributions in their respective fields advance our knowledge, potentially have a profound impact on our lives, and, in the case of the Justice and Women’s Rights Prizes, demonstrate courage and commitment in the face of significant obstacles.

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The Peter and Patricia Gruber Foundation honors and encourages educational excellence, social justice and scientific achievements that better the human condition.  For more information about Foundation guidelines and priorities, please visit www.gruberprizes.org.

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For more information on the Gruber Prizes email media@gruberprizes.org or contact Bernetia Akin of the Gruber Foundation at +1 (340) 775-8035 or by mail 140 W 57th St Suite 10C New York, NY 10019.

Media materials and additional background information on the Gruber Prizes can be found at

our online newsroom:  www.gruberprizes.org/Press.php

Biography – Shigetada Nakanishi

The recipient of the 2007 Gruber Prize for Neuroscience is transforming our understanding of the workings of the brain. It’s not the career his parents had in mind, but this quiet achiever is attracting international attention.
Times were tough in Japan immediately after the Second World War, and in the small rural city of Ogaki, northwest of Nagoya, the parents of the young Shigetada Nakanishi found life more difficult than most. As a result, they became determined that their son would make a difference, would become a useful person.

That’s why they were initially somewhat disappointed when, after earning his degree in medicine, Nakanishi didn’t open a medical practice.

Instead he turned to a PhD in biochemistry and a life of research. “I found myself wanting to know the logical explanation for clinical treatments. At the time it was difficult to explain the mechanism of many diseases and the actions of the drugs used to treat them. I wanted to understand biological systems at a molecular level.”

Forty years on, no one can deny that the recipient of the 2007 Gruber Prize in Neuroscience has made a difference. Now director of the Osaka Bioscience Institute, Professor Shigetada Nakanishi has pioneered the area of communication between nerve cells in the brain. He and his research team have unraveled much of the molecular detail of information transfer and processing. And his work has provided pharmacologists with many new possibilities for drug design.

“A full understanding of the workings of the human brain is still decades or more away,” according to Richard W. Tsien, a member of the Gruber Foundation’s Neuroscience Advisory Board.

“But Shigetada Nakanishi’s work is bringing it closer. He is an unusual researcher who has both created sophisticated tools to help us investigate the brain, and used these tools to make remarkable discoveries about the molecular basis of memory.”

It was during his medical training at Kyoto University that Nakanishi first became interested in how the body was integrated, how information was transmitted between cells and organs. Clearly, the center of this activity was the brain and, where most researchers would have been intimidated by its complexity, Nakanishi simply became fascinated. He decided he wanted to explore the molecular mechanisms of brain function.

Communication between nerve cells depends on chemical compounds known as transmitter substances. When an electrical impulse reaches the end of a nerve fiber it stimulates the release of these compounds, which move across the small gap to another fiber and bind to receptors there. This action either encourages or discourages firing of the second nerve fiber. Nakanishi soon became familiar with the major elements of this process in the brain—the neurotransmitter substances which can excite or inhibit depending on their structure and the receptors to which they bind. But he also became aware of a huge range of other compounds that can regulate or modify the process in subtle ways. And behind the whole system stood the genes that encode the information from which all these compounds are produced.

To increase his knowledge base, in 1971 he went as a postdoctoral fellow to the National Cancer Institute of the US National Institutes of Health in Bethesda, Maryland. It was just at the time that recombinant DNA technology was being developed. “I became extremely excited,” he says.

He began applying those new techniques in a study of the small amino-acid chains or peptides that act as hormones and transmitter substances targeting the nerve cells in the brain and throughout the body. What he found was that one peptide encoded by a single gene could subsequently be split in cells into multiple regulatory hormones.

Using his new techniques after his return to Kyoto in 1974, he similarly discovered several families of transmitter substances, a bewildering diversity of more than 50 compounds with different functions. He guessed there would be an equivalent diversity of receptors to which these transmitters bound. But while techniques existed to isolate and purify the individual transmitter substances, it was difficult to do the same with receptors, which were an integral part of the cell membrane.

The breakthrough came when Nakanishi developed a novel technique for purifying and cloning individual receptors in the egg cells of the African clawed frog, Xenopus laevis. He constructed a complementary DNA (cDNA) library comprising messenger RNA (mRNA) sequences of the brain and injected it into frog egg cells. An mRNA sequence that encoded a receptor would be processed in the frog cell, and the protein-based receptor it produced would become incorporated into the membrane. It would then respond to a small electric current. This effectively disclosed its presence, and the cDNA responsible could be tracked down by identifying increased levels of the same response in fractions of the cDNA mixture.

Using his technique for cloning receptors, Nakanishi and his research team spent many years studying nerve receptors and their interactions with transmitter substances. He was particularly interested in the diversity of receptors associated with the body’s most widespread excitatory transmitter substance—the amino acid glutamate. He cloned and elucidated two broad groups of glutamate receptors—ionotropic, in which the receptor directly controls the opening and closing of pores in the membrane through which ions can pass; and metabotropic, in which the receptor exerts its impact by controlling signaling cascades inside the cell.

“Identifying the molecules involved in brain function greatly helps to solve the question of how information is transmitted and regulated and the integration and processing of information,” Nakanishi says. But he also wanted answers to the question of how nerve cells, transmitters and receptors formed neural networks, the link between different nerve cell types and the receptors they used, and why there were so many different types of receptors. So he used multidisciplinary approaches such as gene targeting, pharmacology, and electrophysiology, and he addressed the processing systems that handle the information gathered by sensory organs, such as the eyes and nose. For example, he found the visual processing system, which used a common transmitter of glutamate, had different types of receptors responding to dark and light. Nakanishi and his team also investigated memory formation and motor coordination.

“But such approaches are not sufficient for pursuing mechanisms underlying integrative brain function and dysfunction,” Nakanishi says. For that quest, he developed another technique, originally exploited in cancer therapy by the man in whose laboratory he worked at NIH, Ira Pastan. Known as cell ablation, it was a means of knocking out specific cancer types which use a particular receptor. Pastan generated antibodies which attached only to that receptor, and carried a toxin to kill the cancer cells carrying it. Collaborating with Pastan, Nakanishi extended this technique to neuroscience and used it to disable all the different nerve cell types in a neural network in turn. The information gained can disclose integrative mechanisms of brain function as well as compensatory mechanisms of brain dysfunction.

Many drugs have their effect by binding to receptors. So Nakanishi’s work in identifying and purifying receptors has been of immense interest to the pharmaceutical industry. Once we know the structure and function of a receptor, it can become a target for drugs designed to stimulate or block it. One set of glutamate receptors in particular, N-methyl-D-aspartate (NMDA) receptors, are associated with not only memory and learning, but also with apoptosis or cell suicide in nerve cells. These have come under special scrutiny.

Nakanishi’s work has been highly acclaimed over the years. His papers are some of the most widely cited in neuroscience. In 1995 he won the Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research, and the next year shared the Keio Medical Science Prize with Nobel Laureate Stanley Prusiner. He was elected to the US National Academy of Sciences in 2000 and became a Person of Cultural Merit in Japan last year.

His parents can be well proud of how useful their son turned out to be.

Written by Tim Thwaites and Niall Byrne, Science in Public, 28 June 2007
For more information about the Gruber Prizes visit www.gruberprizes.org.