Project Objectives

We are here to prepare a report on the Global COE Project Base. We’d like to hear from Professor Yasushi Miyashita, the project leader of “Integrative Life Science Based on the Study of Biosignaling Mechanisms,” and Professor Hiroo Fukuda, a core member of it.
First of all, please describe the objectives of the project.

Professor Miyashita：

We aim at establishing a university-wide, comprehensive group that covers all research and educational activities in life sciences in The University of Tokyo, and creating a crucible for nurturing young researchers who will become international leaders. Here at The University of Tokyo, many important studies have been undertaken, but they have tended to lack intimate cooperation and unity. Although this problem of disunity has been solved to the extent of unification within individual departments in the context of 21st Century COE projects, we have been unable to integrate the departments to form a network that involves our university as a whole. I hope that such a research and educational system will be realized in the present Global COE project.

For the last two years, the trend of development has been toward concerted research activities throughout The University of Tokyo. Before our Global COE project was implemented, two organizations, namely the Network for Life Sciences Research and the Network for Life Sciences Education, went into operation at the initiative of the president. Professor Fukuda here is the director of the Network for Education. It should be noted, however, that these two networks cannot operate well without a core center that bridges their activities. Our Global COE base should serve that purpose.

Professor Fukuda：

From the viewpoint of the Network for Education, it is quite difficult to solve the problem of how to unify the educational and research programs for students in The University of Tokyo as a whole. One of the hurdles to clear is over-compartmentalization. As suggested by Professor Miyashita, the present COE project represents our first attempt to organize a unified research and educational system across the departments and sections.

This Global COE base consists of three organizations, namely, the Graduate School of Medicine, the Graduate School of Science, and the Institute of Molecular and Cellular Biosciences, doesn't’t it?

Miyashita：

Yes. The majority of the groups in our Global COE project are working in the area of basic biology, but some are engaged in basic medical research into diseases and pathologies, research that will lead to direct contributions to society. Specifically, some groups are investigating cancer or nervous diseases. Hence, the Global COE project covers a broad range of themes, from basic research to preclinical studies. This is a groundbreaking fact. It’s likely that no comparable system existed in our university in the past.

Fukuda：

In other words, the Global COE project can be described as a system that allows us to deal with the common principles in life on the basis of research into a wide variety of organisms. This is a time when a number of tools are available for exploring organisms from the same viewpoint. In particular, one can study and discuss all organisms in the context of the genome.

A broad range of investigational materials, from yeast to mice and monkeys, is used in the Graduate School of Medicine, but the ultimate goal of the research activities there is to elucidate human functions and pathologies. As for the situation in the Graduate School of Science, the subjects of research are even more diverse, ranging from yeast to plants and animals, and the animal subjects include a very wide variety of organisms, such as honeybees, fish, and birds. Now researchers at the Global COE base are able to explore human being on the basis of findings related to diverse organisms. Our COE project is excellent at clarifying the principles shared by all organisms and teaching them to young people. It is certain that these objectives are now much easier to accomplish than before.

I suppose that even if researchers representing a variety of areas get together, they won’t necessarily act quickly as a group. 　

Miyashita：

Special efforts are necessary to see that such a transversal organization operates smoothly. First, we organized our system with distinct themes like the warp-and-weft structure of fabrics. The weft consists of four component research topics, namely development of life, functional control of life, relay of generations, and abnormalities of living systems. The warp serves as a linker for researchers who belong to different departments or sections. The philosophy underlying our Global COE project is directed at sharing methodologies, sharing themes, and sharing objectives.

The sharing of the themes pertains to the four items I have just mentioned, namely, development, functional control, relay of generations, and abnormalities of living systems. Additionally, since we live in an era of innovation, developing and sharing new methodologies is of paramount importance. In fact, no method spreads readily to other relevant areas from the area where the method has been developed. Although developers of highly advanced methods are available in The University of Tokyo, those methods are likely to localize.

Would you please give some specific examples to facilitate my understanding?

Miyashita：

OK. For example, multiphoton imaging is a powerful tool that allows one to visualize submicron structural changes in living cells without fixation treatment, and this method was developed by a faculty member at the Graduate School of Medicine. However, it is quite difficult to operate the apparatus in actual experimentation, because both sophisticated femtosecond laser technology and efforts to control organism-derived fluctuation are required. If researchers in different areas share this and other highly useful methods, life science research in The University of Tokyo as a whole will be further upgraded.

Earlier you mentioned the slow progress of the spread of new methodologies. Why is that? Is it because the research has been conducted within the narrow world of the laboratory?

　　　　

Miyashita：

No. Today, researchers have broad international communication via web or email, or frequently at international congresses. But it should be noted that researchers have almost no opportunities for conversing personally with other researchers of different research areas in the University. All researchers are aware that it is unrealistic to expect satisfactory communication via today’s electronic approaches and that this situation calls for emphasis on face-to-face communications. Unfortunately, however, most researchers are apt to experience personal communication only at international and domestic congresses held in their specialties. So the question is how to realize communication among the researchers across their different areas and specialties? In this sense, our Global COE project is highly promising. Of course, this form of communication is necessary for both faculty members and students. We have incorporated a mechanism for this idea into our Global COE project in the form of retreats, for examples.

Internationalization and retreats

What are the improvements being made in the Global COE project compared with the 21st Century COE projects?

Miyashita：

We have been planning for a long time to internationalize the research and educational activities in The University of Tokyo. Of course, research activities have been globalized for a long time now, but the concept of globalization cannot be introduced into educational programs for graduate students without a range of special efforts. It’s not useful for students to take, through the medium of their faculty members, the one-way street of working at overseas research institutions in Europe, the US and elsewhere. Two-way, internationalization-oriented education at the organizational level must be provided.

One of the major objectives of the Global COE project here is to nurture internationally minded young leaders, and to this end, we position our retreats as an opportunity for their systematic training.

Perhaps you could describe what you’re planning to do.

Miyashita：

In the past, retreats were tested in the 21st Century COE projects. In those retreat sessions, faculty members and graduate school students gathered at one location, leaving their usual research setting, and had free and generous exchanges of opinion beyond the barriers of class-level and generation, usually in a one-night stay. First, we are going to internationalize these retreats.

We invite young researchers from overseas research centers, including independent researchers called principal investigators, postdoctoral researchers, and, as the case may be, even graduate students. These people are invited to make poster presentations and join discussions at our retreats. We intend to introduce the concept of sharing the methodologies I have just talked about, not only within our base but also at the international level.

On the other hand, students are dispatched from our GCOE base to retreats at overseas research organizations. Two-way internationalization is important.

Your first cooperation will be with the University of California at San Francisco (UCSF), won’t it?

Miyashita：

Yes. UCSF is a world-class research center in the field of life sciences. UCSF’s retreats are very large-scale, and provide many sessions concerning different themes in biology such as neuroscience, cell biology and immunology. The UCSF retreats involve overnight stays. Graduate students in our Global COE project go there, make poster presentations about their own studies, encounter criticism, build up counter-arguments, criticize their opponents, and engage in overnight discussions. This is a bit like a knight-errantry.

The internationalization committee in our COE project approaches the UCSF to make the necessary arrangements, including time schedules, and our students participate in the retreats on a formal basis. Some of the students at my laboratory already joined a UCSF neuroscience retreat some two months ago, and they seem to have had some hot arguments that provided valuable experience in terms of both friendship and competition.

How long do your students stay there for such retreats?

Miyashita：

Usually, each retreat continues over two or three days. On the last occasion, our students made additional visits to some of the labs that had joined the retreat, thanks to a formal referral by UCSF. In such cases, several more days are taken after the end of the retreat.

So, the participating students are able to meet a considerable number of researchers, aren’t they?

Miyashita：

That’s right. After meeting about 200 persons at the retreat, they visit five or six labs including the host lab. Combining these opportunities, our students meet a great many people. It is also meaningful for the students to visit labs and make oral presentations there to communicate with people who did not attend the retreat. There is a difference between poster and oral presentations. For this reason, lab visits are very significant in their own right.

The participating students are required to submit reports after returning home, aren’t they?

Miyashita：

Yes. And those reports are kept by the Global COE committee in a publicly accessible way on our website. Of course, we make sure there’s adequate follow-up.

In our COE project, students do not go abroad on their discretion, but they are dispatched under the control and responsibility of the committee. As such, the programs offered are hard for the participating students, but are worth joining.

Fukuda：

For young people, it is very good to have more opportunities to converse directly with researchers abroad. Now I would like to add a few words to what Professor Miyashita said. In the 21st Century COE projects, we proceeded by trial and error to provide our students with overseas personal exchange programs. In planning the present Global COE project, we have been able to make use of our experience in the 21st Century COE. This success wasn’t achieved in one day, but was realized through sincere, steady efforts and much experience in international exchange by the researchers involved in past projects. Our retreats are also offered on a satellite basis as required. Last year we had a satellite retreat with the participation of about 120 people, mainly in the Graduate School of Science.

Education for graduate students

It’s clear that retreats represent one of the pillars of your educational program for graduate students. Now, what other kinds of things are you doing at the Global COE base here?

Miyashita：

First, I would like to describe our lecture system. We have created a system that allows students both in the Graduate School of Science and the Graduate School of Medicine to take the same lectures by top researchers from abroad, and arranged other for-credit lectures for both of them. This is one of the merits of the cooperation between the two graduate schools. Another merit is the seminars. A great many seminars are given by prominent lecturers, both domestic and overseas. We have built an information network to concentrate all information on the seminars in the educational program committee, from which liaisons are e-mailed to all people concerned, including students.

How about the sharing of methodologies?

Miyashita：

Since it’s not enough simply to have lectures and seminars, we have established a new training course system for practice. Students can make the first step toward learning a new method only when they are involved in actual experimentation using the method. Every training course is open to all members of the Global COE project, including students, although participants are selected by lottery, since there are limitations in facility availability and so on.

The length of a training course varies depending on its content, and each course lasts for two weeks or so. Sessions take place every day, and up-to-date skills are taught in well-designed curricula. We support students so that they can make personal connections with the host lab for the sake of their own research experiments in the future. Of course, simply completing the 2-week course does not immediately lead to the development of a student’s ability to do experiments by him or herself, but the barrier is much lower when the student is actually doing experiments.

Could you give some examples of specific training courses?

Fukuda：

In the Graduate School of Science, we are planning to provide biodiversity research training using a wide variety of marine organisms at the Misaki Marine Biological Station.

Miyashita：

In the Graduate School of Medicine, we will teach new techniques in cell biology and electron microscopy, and new imaging techniques at the individual level using MRI for human subjects. We believe these hands-on trainings are necessary to ensure that the activities promoting the main theme of human resources be realized.

Example studies

Would you give some specific examples of the research activities? 　　　

Miyashita：

Basically, all investigations are undertaken with a focus on biosignals. There are two types of biosignals, intracellular and intercellular, with calcium being typical of intracellular signals. In the context of the sharing of methodologies, the first to deserve mention is imaging for visualizing calcium behavior in the body. This also applies to multiphoton excitation.

Now may I ask a very simple question? What is meant by the term “imaging”?

Miyashita：

For example, it has been traditional practice for biochemical researchers to collect and squash tissue samples before quantifying the enzyme activities or concentrations of other biosignaling molecules in individual cells and cell populations. This tells them, for example, whether calcium is present in the material and whether the calcium concentration is high or low. However, the squashing step makes it impossible to examine spatial and temporal dynamic patterns and changes. Hence, beyond simple abundance of a particular substance, importance should be placed on biological dynamics to determine the spatial patterns and temporal changes in the substance.

By doing so, you can learn what’s happening in different portions of various types of cells.

Miyashita：

There is a very wide variety of cells. For example, nerve cells are morphologically very complex. Typically they have long thin axons and long bizarre extruding dendrites. You cannot locate the chemical reactions in the complex dendrites if the specimen is squashed as usual. Instead, in imaging, you create molecules that allow the visualization of the reactions, inject them into cells, and watch the reactions by, for example, exciting the molecules by means of laser. Japan leads the world in this technology.

I see. So the idea is to visualize the reactions without squashing the samples.

Miyashita：

Yes, but meanwhile, there are numerous important things that cannot be visualized without squashing the samples, so the methods are complementary to each other. As a tool for visualization, microscopy is available, and it involves a broad range of techniques, from electron microscopy to multiphoton excitation microscopy based on a sophisticated application of laser technology, and also magnetic resonance imaging for the determination of individual functions by means of NMR signals. It is also necessary to develop and operate molecular biological approaches for the molecules and tissues that are the subjects of visualization. Both microscopy experts and molecular design professionals are available in The University of Tokyo, but none of them have both capabilities, so working jointly is of paramount importance.

More generally, basic research must be undertaken in two ways. One is toward developing new methodologies to advance the cutting edge, and the other is directed at interdisciplinary or unified investigations. One-sided research is unacceptable. Overemphasizing interdisciplinary aspects can lead to superficiality, and pursuing the cutting edge of methodology leads to excess specialization. As history tells us, new methodologies emerge from widely different areas.

Fukuda：

Such joint research activities by the Graduate School of Medicine and the Graduate School of Science have already produced excellent results. Professor Kensaku Mori at the Graduate School of Medicine and Professor Hitoshi Sakano at the Graduate School of Science jointly clarified part of the mechanism behind neurotransmission in the olfactory nervous system of mice. Until that time, little had been known about how odor signals are transmitted. The cooperation of those two men beyond the boundaries of their departments resulted in the elucidation of the points of entry and destinations of different odors in the nervous system.

　　　

Messages for society

Finally, what message might you have for society at large?

Miyashita：

First of all, we must aggressively address the importance of supporting basic research in society. In particular, our Global COE project is not directed at finding immediate applications for research results.

Of course, on a long-term basis, many important applications will be found. Let’s take an example of basic research of cancer. In cancer research, investigations are undertaken at various levels. Some concern mechanisms for the initial mutagenesis, and some concern mechanisms for the later development and metastasis of cancer, and others want to discover new principles for treatment of cancer. It should be noted, however, that our Global COE project does not aim at cancer treatment of patients, which is a task for clinical medicine. We are endeavoring to elucidate the basic molecular and cellular biology mechanisms behind carcinogenesis, and the mechanisms for metastasis and malignancy.

And there is the matter of accountability, isn’t there?

Miyashita：

Yes. We must be accountable. In other words, we are obliged to explain the content of our studies, their potential for future applications, and their current status in relation to the potential. We hope that society will respond favorably to our activities. To this end, how to provide society with information is quite an important issue.

Although there is a place for investigations that immediately find valuable applications, assessing investigations based solely on their immediate utility would lead to errors. Rather, excellent applications emerge in the end from still more basic research. This is what history tells us.

In recent years, it has become evident worldwide that developing countries, including China, India, and Iran, have become conscious of the importance of basic research areas, particularly in biosciences, and have begun making vast social investments. For example, giant clusters of modern research institutes have been born in Shanghai and Singapore. In these countries, researchers who earlier went out to foreign countries are beginning to return home. I want to let everyone know that these events are occurring all over the world.

In a previous era in Japan, it might have been sufficient to think about applying what has been learned in other countries, but now?

Miyashita：

Today, Japan must have strategies or grand designs on basic research that cover periods of 10 years, 20 years, or even 50 years. Essentially, success in learning depends on originality and breakthroughs. I believe Japan will not survive the global competition in the future without strengthening its basic research and nurturing human resources that will become international leaders.

Fukuda：

I agree with Professor Miyashita’s thinking. Any attempt to do something with a superficial view would lead to errors due to the complexities of life behind them. I believe one cannot achieve an application in the true sense unless the basic principles of life are fully understood. Hence, we want to elucidate the basic principles of life in the Global COE project. Social communications are also important. Of course, we are determined to be positive in opening up to society the findings and useful information obtained through our research activities, and I think another very important form of social communication is to send young researchers who will be the driving force in the coming generations out into society. In terms of the coverage and depth of life sciences research, we probably beat all other groups. In this situation, we want to nurture researchers who will support and drive basic research in life sciences in the coming generations.

Thank you very much for granting this interview in the middle of your busy day.

(Interviewer: Masaharu Yano, COE Program Promotion Office)