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In Pursuit of the Construction of  “Biological Nanomachines”

From OU, and Back Again

Distinguished Professor Keiichi Namba first began thinking that he wanted to become a researcher when he entered junior high school. He was amazed at all the mysteries of the natural world. He also had a strong interest in physics and the structure of living things, so he found himself interested in biophysics, to which his former high school teacher suggested that he enter into the Biophysical Engineering Department of the School of Engineering Science at Osaka University.

In the early days of the School of Engineering Science, Professor Namba was able to take leading-edge courses in a variety of fields in order to solidify a broad foundation for his knowledge. Professor NAKAMURA’s statistical thermodynamics course was a masterful course with an intro, development, turn and conclusion, and yet the text from that very class is something he still always has by his side. Something noteworthy came from Professor OHZAWA Fumio’s molecular biology course. When rereading the notes from this course, Professor NAMBA’s research theme was recorded inside. "I'm impressed to see the results of the research that I met with and cultivated at OU even now."

True Form, Not a “Dried Husk”

 Professor Namba’s main topic in graduate school was muscle contraction. Said the professor, "I wanted to view this mechanism from its molecular structure." The electron microscopes at the time simply involved looking at dried materials by shooting an electron ray in a vacuum, like observing a “dried husk."

In order to view the natural form of a specimen, the only option was x-ray analysis, but this required crystallization of the specimen. However, crystallization of complex fibrous proteins such as muscles is a difficult task. Research continued on with a bit of ingenuity, but it never reached the point of viewing molecular structure at the atomic level.

In order to take on this problem, Professor Namba plucked up the courage to speak with Professor Donald Caspar at Brandeis University, well known for his research of the three-dimensional conformation of viruses, and through a stroke of luck, he landed a position as a researcher. In the USA, he successfully performed structural analysis on the tobacco mosaic virus (TMV), and the method for doing the same for non-crystallized fibrous proteins such as muscles came into view.

At around the same time, in 1986, Professor Namba came upon then Japan Science and Technology Corporation’s ERATO project. This was the meeting that led him into flagellum research. What greatly changed his course after that was a cryo-electron microscope developed by Professor FUJIYOSHI Yoshinori (currently Specially-appointed Professor, Nagoya University). It was then that his research on viewing the “true form” of specimens by freezing them to ultra-cold temperatures began.

Biological NanoMachines and Their Future

The flagellum and the rotating motor at its base are made up of nearly 25 different proteins. In order to view this structure, x-ray analysis methods and technology, as well as cryo-electron microscopes, need to be developed, and through a complimentary combination, it became possible for the first time.

Professor Namba, while leading research projects from Matsushita Electric Industrial (now Panasonic) and the ERATO project, through the course of months and years of effort, was finally able to clarify the composition of flagella at the molecular level. He also advanced the development of technology of the cryo-electron microscope and image analysis, meaning analysis of the conformation biological molecules that used to take researchers years to obtain could now be obtained in just a week. This lead to a huge development in biological science.

Also, using these methods and technology, Professor Namba succeeded in getting a clear picture of the structure of complex fibrous proteins used in muscle contraction, a long-standing challenge. “It took me 30-odd years from my time as a graduate student, but I finally succeeded, albeit a bit unceremoniously,” he said.

On top of that, Professor Namba had his hand in the development of an image noise-reducing filter to be used in cryo-electron microscopes. Said a bright-eyed Professor Namba, “Observations with resolution under 0.2nm are right before our very eyes.” When this happens, not only will the conformation of high molecules such as proteins become visible, but various ions and the water molecule H2O, which bonds to proteins and plays a critical role, will also become visible. The progression of these explanations will serve as valuable weapons for future drug development technology and prognostic medical care.

The expansive future of biochemistry can be found in the tiniest nanomachines that have finally become visible through Professor Namba’s research.

 

If You Hold a Strong Will, Your Passion Will Show Through

It takes a long time to obtain results from research. If you don’t hold a strong interest in what you’re doing, you can’t continue. But, “if you’ve got interest and curiosity, there is no job more enjoyable than this,” proclaimed Professor Namba. If you hold a strong will, your passion will show through to others. Other people and groups will support you, and your chance will come. “Research is discovering mysteries and solving them. I’m just happy I could give my life to such a wonderful profession.”

 

About Distinguished Professor Keiichi NAMBA

A 1974 graduate of the Osaka University School of Engineering Science, Professor Keiichi NAMBA obtained his doctorate from the Graduate School of Engineering Science at Osaka University in 1980. After serving as a researcher at Brandeis University and Vanderbilt University in the USA, in 1986, he became a group leader on Professor Hotani’s supramolecular flexible structure project. In 1992, he served as a research director at Matsushita Electric Industrial (now Panasonic) International Research Institute and Advanced Technology Research Institute. In 1997, he also began working on then Japan Science and Technology Corporation’s ERATO Namba Protonic Nanomachine Project as the director. Professor Namba became a professor at Osaka University’s Graduate School of Frontier Biosciences in 2002, and the dean in 2010. After serving as the chairman of the Biophysical Society of Japan, and winning the Osaka Science Prize, the Association for Technological Excellence Promoting Innovative Advances Grand Prix Best Picture Award, and the Imperial Prize of the Japanese Academy in 2012, he became an Osaka University Distinguished Professor in July, 2013.

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