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Aiming for biomedical strategic development at the only overseas research base of a Japanese university

Waseda BioScience Research Institute in Singapore (WABIOS)

Singapore, a small country with almost no natural resources such as energy or water and food, has strived to become an Asian economic hub through its own international economic and trade policies. In recent years, it has developed growth policies through established bold science and technology innovations targeting next generation and more advanced generation fields. One field in which they have especially put efforts into since 2000 is the biomedical field.

In the biomedical field, in order to enter markets, be it with pharmaceuticals, new treatment or examination methods, or manufactured goods, it is necessary to undertake and have recognized clinical tests that abide by the safety standard rules of each country. These differ from country to country, but a long time is required in making products starting from basic research through to clinical tests. In Japan, about 10-20 years is required in the production of new medicine. In order to somehow speed up this process, both a research environment and clinical test capable systems are essential in leading biomedical research.

In Singapore, at the same time as setting the biomedical field as a strategic target, consistent software infrastructure systems in order to strategically promote areas from basic research to clinical tests to manufacturing products have been installed. If clinical tests can progress smoothly in Singapore, the data is then taken back to each country and can be used as predominant material in order to rapidly advance development and judgment for approval in those countries. This predominance is becoming a driving force in attracting companies and academic research bases from around the world. At the same time as aiming for innovations from basic science and gathering top-class researchers from the world over, Singapore has lured world famous pharmaceutical companies and pharmaceutical goods industries, and succeeded in setting up clinical test and production bases.

In Tuas Biomedical Park (opened in 2000), an industrial estate for the biomedical industry built on the westernmost tip of Singapore, Pfizer, Novartis, Merck Sharp and Dohme, Roche, GlaxoSmithKline, and Abbott.companies in the world's top 10 pharmaceutical companies, have set up production bases. At Biopolis (opened in 2003), an integrated base for research and development functions built on the outskirts of central Singapore, as well as housing the national research center, Singapore Agency for Science, Technology and Research (A*STAR), businesses, universities, and government affiliated research organizations from around the world have established biomedical research and development bases. On top of that, the new integrated base, Fusiono Polis (opened in October 2008), with a set strategy of interdisciplinary creation and development between the fields of bio and physics, chemistry and engineering, was established, with many organizations, both domestic and international, being housed here as well.

As the only Japanese university to enter these international integrated bases with a research base, Waseda Bioscience Research Institute in Singapore: WABIOS has set up its base in Biopolis. In regards to the aim from entering Singapore and research strategy, we spoke to WABIOS head, Professor Shinichi Ishiwata, Faculty of Science and Engineering.

"Biopolis" housed in WABIOS. Of the nine research buildings completed by 2006, five are occupied by national organizations under the A*STAR umbrella, and four house international industry, government and academia research facilities. In addition to these, a research building was newly opened in 2010 with translational research and medical technology / medical equipment research as its target. It is planned to become a 330 hectare major integrated base by 2013. (Photographs from Singapore Economic Development Board material)

WABIOS head, Professor Shinichi Ishiwata, Faculty of Science and Engineering

As a new base for "Asian Waseda"

The entry of a Waseda University research base in Singapore can be traced back to 2004, before the opening of WABIOS. The origins lie in, as well as a request from the Singaporean government, the establishment of the Waseda Olympus Bioscience Research Institute (WOBRI) in Biopolis, which was jointly financed by Waseda University and Olympus Corporation.

"For 5 years from 2004, through research related to neuroscience, starting withA*STAR,we built solid foundations for joint research systems with research organizations and universities in Singapore. When the WOBRI project finished in April 2009, after six months of deliberations, it was decided that Waseda University would continue to maintain a research base independently. Our dealings up until then had laid the groundwork, and WABIOS activities began." (Professor Ishiwata)

It is unprecedented for a Japanese university to independently place a research base overseas. All the more because it was a cutting-edge field, there are great investments required and success risks that are omnipresent in research and development, so it was not an easy decision to make. However, the results of connections built in Singapore were a huge asset. For Waseda University, which does not have a medical faculty, conducting international joint research with medical researchers from Singapore and other countries presents a great chance for us to develop the biomedical field.

"There are already many people in our Faculty of Science and Engineering who are involved in life science as a fundamental science. Domestically, we are already undergoing creation of joint research bases such as ASMeW (Consolidated Research Institute for Advanced Science and Medical Care) /TWIns (Center for Advanced Biomedical Sciences), with the aim of integrating medicine, science and engineering. Furthermore, the creation of a base in Singapore can be said to be a necessary development for our university which has historically been aware of Asian universities, has deep relations with key figures from various countries, and has connections with well-renowned universities. On top of East Asia, the creation of a wide Asian network including Southeast Asia and Australia, we thought this would become an important base." (Professor Ishiwata)

In July 2011, we were selected for Waseda University's Research Initiative Program, securing research funding which is hotly competed for within the university, adding momentum to the startup.

Research base for life sciences putting to use the backbone of science and engineering

The WABIOS research strategy is to promote interdisciplinary research of the life sciences by integrating physics, chemistry, information science and medical science. Specifically, three groups are proceeding with research activities based on the four themes of (1) physical biology, (2) nano-biotechnology, (3), bioimaging, and (4) chemical biology.

3 research groups are active at WABIOS

For example, in the field of physical biology, where research is going ahead in estimating the "temperature" and "strength" of a single cell and understanding phenomenon seen in cells from a physics viewpoint, unique research and development, a concept called "inner-cell walking nano-thermometer" is taking place. With the world's highest resolution and method that can measure temperature change and distribution at high speeds, we have succeeded in simultaneously measuring inner-cell temperature change and cell functions (announced in March 2012). In science up until now, temperature distribution in cells has been considered as irregular and abstract. However, if we can measure these minute level temperature changes and link them to biofunctions, there is a greater possibility of linking them to the understanding the mechanisms of the onset of cancer etc. and the discovery of new treatment methods.

"Fluorescent dye was covered in polymer and fluorescent nano-particles that react to heat only were developed. Just by sprinkling these on the cell, they are naturally absorbed into the cell, and on top of that, motor protein sticks to the absorb vesicle and walks around in one direction on microtubules (tubular protein polymer) inside the cell. The molecular motor accelerates and decelerates in accordance to the temperature change, walking and monitoring the temperature in each area. Our next issue is to improve sensitivity measurement. At the current stage the resolution is 0.3℃, but we want to raise that up one place. We must try to technically improve the measure method." (Professor Ishiwata)

Concept of the fluorescent nano-thermometer

A:Nano-thermometer walks in cell, B:High resolution mapping of observed positions and movements

In the domain of nano-biology, while working with researchers from Singapore, we are putting a lot of effort into artificial red blood cell research and development. Artificial red blood cells are used for organ storage and regenerative tissue engineering etc., and they are of high value for support in times of natural disasters and emerging infectious diseases. With cooperation from the National University of Singapore Faculty of Medicine and Faculty of Engineering Bioengineering Department, administration tests on animals are being planned.

"Blood collected from blood donations cannot be preserved and a large proportion must be disposed of, but by extracting hemoglobin and adding an artificial membrane it becomes possible to store, and we are developing artificial red blood cells with oxygen transport mechanisms for practical implementation. There are others conducting artificial red blood cell research, but I believe we are the only ones to achieve the same oxygen transport mechanisms as real red blood cells and a high degree of safety." (Professor Ishiwata)

Research and development of artificial red blood cells using hemoglobin

A new research group was established in December 2011, and is comparing phenomena inside healthy and sick cells, and searches for differences by designing and developing molecular probes in the domain of bioimaging. The developed molecular probe is even used in the chemical biology field with the aim of establishing new diagnosis methods such as finding substances that control phenomena that become the cause of diseases, and the discovery of therapeutic drugs.

In a fascinating yet strict environment

Symposiums and seminars are frequently held at Biopolis, and there are opportunities to meet fellow researchers and exchange information on a daily basis. A researcher database that can be searched on internet is kept up-to-date, providing an environment that promotes joint research.

Every year, the Singaporean government invites applications for a project on the theme of strategic research, and contributes large-scale funding to the value of 10 billion yen to one group over 10 years. A big aim of overseas research organizations setting up bases in Singapore is to form a new joint research project and secure this type of government funding.

"What especially surprised me is that the government of Singapore even allocates large funds to unique fields like mechanobiology. This is extremely advantageous to research bases like ours that have the potential to merge medicine and science and technology. This applies perfectly to research and development searching for worldly physical properties in blood vessels, muscles and cells, the aim of the physical biology field." (Professor Ishiwata)

As a first step, in 2012 we started the "Bioelectronics" project, a joint research project with Nanyang Technological University's Assistant Professor Hirotaka Sato. The same project, as a subsidized project in conjunction with A*STAR and the Japan Science and Technology Agency (JST), receives a $300,000 SGD subsidy for each group over the three year period of 2012-2014.

"Bioelectronics" project where biochips are implanted in insects and the insects' movements are controlled via electronic signals. Expectations have been raised with the new joint research of "Cyborg Insect" research conduct by Assistant Professor Hirotaka Sato (Waseda University graduate), Nanyang Technological University, and Professor Ishiwata's group which majors in muscular biophysics.

A major aim of WABIOS is also to train internationally-minded personnel. Targets in strategic fields have been narrowed down and have been the object of a small number of personnel exchanges and cooperation. We have already ready entered into exchange agreements with research organizations and universities in Singapore since a few years back. We have also entered a research exchange program (A*RAP) with A*STAR, and established systems where Waseda doctorate students can receive guidance at Singaporean research organizations while earning credits for Waseda degrees etc.

"On the other hand of Singapore gathering people from around the world with attractive themes, evaluations are also very strict and employment conditions aren't tempting. When policy lines or research strategies change, there are many cases where even people who have moved from overseas for their job are mercilessly dismissed. Of course they are prepared for that when they come though. Learning in that type of environment is definitely a huge stimulus for young researchers from Japan." (Professor Ishiwata)

Activities at WABIOS, as a pilot project coming from Japan, are getting a lot of attention from both within the country and overseas. In this diverse interdisciplinary and international expansion that is not possible in Japan, there is hope being carved out that that basic research, of course in the biomedical field, will possibly lead to practical developments in urgent global issues such as the environment and energy.

Related links

Waseda BioScience Research Institute in Singapore (WABIOS)
Organization for University Research Initiatives, Waseda University
Faculty of Science and Engineering, Waseda University
Singapore Agency for Science, Technology and Research (A*STAR)
National University of Singapore
Nanyang Technological University