IN FOCUS
Heritage For
The Future
CONTENTS
2-Heritage for the Future Osaka builds on its legacy in the biosciences
© 2011 by The American Association for the Advancement of Science. All rights reserved.
18 February 2011
1
OSAK A I N F O CU S
Osaka has been at the center Kishimoto Foundation to support research. I the Ãrst simultaneous heart-lung transplant
of Japans pharmaceuticals industry since want to contribute to nurturing the next gen- in 2009.
the 17th century when the Doshomachi dis- eration of researchers in the life sciences, So what are the plans for Osakas return
trict was a hub for merchants trading herbal says Kishimoto. to center stage?
medicines. The area has been an incubator In the area of infectious diseases, the dis-
for global companies like Takeda Pharma- covery of Vibrio parahaemolyticusa bac- Developing a Strategy
ceutical Co., Ltd. and Shionogi & Co., Ltd, terium that causes food poisoningwas The core goals, which are contained in the
as well as the predecessor of Osaka Univer- made at the universitys Research Institute so-called Osaka Bio Strategy, involve ac-
sitys School of Medical Sciences. for Microbial Diseases (RIMD), and its broth- celerating the development of new drugs
Osaka has a rich history of research in er institute, the Research Foundation for and medical devices; promoting construc-
the life sciences and is a base for major Microbial Diseases (BIKEN), Japans largest tive alliances between industry, academia,
pharmaceutical companies, says former manufacturer of vaccines for diseases such and government throughout the Kansai area
president of Osaka University and immu- as chickenpox. Notably, scientists at RIMD (which includes the cities of Osaka, Kyoto,
nologist Tadamitsu Kishimoto, currently a are also developing vaccines to Ãght malaria, and Kobe); and strengthening support for
professor at the Graduate School of Frontier a so-called neglected disease, which affects venture capital companies (via the Osaka
Biosciences, Osaka University. Biomedicine about 40 percent of the worlds population, Bio Funds ¥1.1 billion ($13 million) in capital
has tremendous potential here. We want to mostly in poorer countries. assets). The establishment of a Compre-
realize the dream of former president Yuichi The tradition of pioneering work in immu- hensive Global Strategic Special Zone of the
Yamamura, who envisaged Northern Osaka nology, initiated by the late Yuichi Yamamu- Japanese government is included, with two
as an international hub for life sciences. ra, is being continued by Osaka Universitys core priority areas: the biomedical industry,
Indeed, Osaka-based scientists have Kishimoto and by Shizuo Akira, director of and environment and new energy.
made outstanding contributions to the the Immunology Frontier Research Center Participation is being sought from some
life sciences including the discovery by (IFReC) whose research on Toll-like recep- of the worlds largest electronics, chemical,
Kishimoto of interleukin-6 (IL-6), a protein tors, innate immunity, and viral recognition and precision instrument companies, such
governing the immune response. This led has made him one of the most highly-cited as Panasonic and Sharp, both of which are
to the development and commercialization immunologists. headquartered in Osaka.
of the IL-6-inhibiting drug, tocilizumab, for Breakthroughs have also been made The biomedical industry relies on medical
the treatment of Castlemans disease and in transplant surgery at Osaka University devices, says Yasushi Sugimoto, director
rheumatoid arthritis. Kishimoto donates the Medical School, where surgeons performed general of the Department of Commerce,
proÃts from the sale of tocilizumab to the Japans Ãrst kidney transplant in 1964 and Industry and Labor, Osaka Prefecture. The
Tad o
a mitsu Kishimot
Kansai region is Japans largest manufac- its expertise in protein research, exempliÃed of its principle investigators are foreign, a
turer of lithium ion batteries, generating ¥22 by more than 50 years of research conduct- rare situation in Japan, but made possible
billion ($260 million) in revenue in 2009, and ed at Osaka Universitys Protein Research through extensive support provided by IF-
batteries are a critical component of medical Institute (PRI). Now, in an innovative devel- ReC staff for foreign scientists to help them
equipment. opment, the biomedical cluster launched overcome language and cultural barriers.
To promote interdisciplinary and cross- the Protein Mall in May 2009 as an open
sector collaboration, the Osaka Bio Head- access platform for drug discovery. It aims Looking to the Future
quarters has been set up to bridge the gap to create a drug development value chain There are some disturbing trends among
between research and commercial entities. to foster business opportunities based on young Japanese researchers that worry
The Bio Headquarters consists of members protein-related research. their senior counterparts. Youngsters are
from industry, academia, and government, Knowledge is essential, but collaboration reluctant to go overseas these days, notes
says Kishimoto, president of the organiza- is also critical to achieve Osakas goals. Kishimoto. Its probably because Japanese
tion. Members of this organization devise As such, the Drug Seed Alliance Network universities now offer world class research
plans to achieve our goals as part of the Japanmanaged by the Osaka Cham- environments. But research is not only
Osaka Bio Strategy framework. ber of Commerce and Industryis actively about equipment and clean rooms; meet-
To provide support for venture compa- promoting partnerships between industries ing people from different backgrounds and
nies, the Osaka Bio Strategy includes the both within Japan and overseas. Recent in- developing international networks is equally,
launch of a biotalent matching service cater- ternational agreements include memoranda if not more, important.
ing to the human resource needs of start- of understanding signed with France, Aus- Only time will tell how these trends will af-
up companies. tralia, Belgium, and the BioBusiness Alliance fect Japans research prowess, but the new
of Minnesota. research programs have attracted many
Promoting Research, Fostering A central and important facility in the bright researchers from overseas, which
Business Northern Osaka Bio Cluster is the National may compensate for the decreased willing-
To reduce both the time and cost of per- Institute of Biomedical Innovation (NIBIO), ness of Japanese scientists to travel inter-
forming clinical trials, Osaka plans to make which the government set up in 2005 to nationally.
available the expert services of institutions act as a stepping stone for commercializing Osaka and the Kansai region have a lot
such as the Ãve hospitals of the Osaka ideas from the laboratory and bringing them to offer the biomedical industry with new
Prefectural Hospital Organization to the into the clinic. Research at NIBIO ranges projects in neuroscience, human-machine
pharmaceutical industry. A clinical trials from developing adjuvants for more effec- interface research, cancer treatment, and
website has also been set up, offering up- tive vaccines to maintaining an ancestry robotic assistance in hospitals, all of which
to-date information about trial results. On database of cynomolgus monkey colonies, build on the legacy of Osaka's pharmaceuti-
the policy side, a request has been made which is openly available to researchers. cal and electrical industries.
CREDIT: (LEFT) © ISTOCKPHOTO.COM/SIMFO;
(RIGHT) © ISTOCKPHOTO.COM/SHUNYUFAN
by the Osaka Bio Headquarters to the The strength of Osakas expertise in life On balance, the important fact is that Osa-
central government and the Pharmaceuti- sciences is based on decades of basic re- ka is still an energetic and forward-looking
cal and Medical Devices Agency to make search conducted by imaginative and highly location for pursuing research and business
positive reforms to clinical trial regulations motivated scientists, historically from within in the biosciences.
and practices. Japan but now also from overseas. Shizuo
Knowledge of the properties of proteins Akira, director of IFReClaunched in Octo-
is extremely important for fundamental re- ber 2007 as one of only Ãve World Premier Adarsh Sandhu holds joint professorships at
search on immunology, cancer treatment, Institutes chosen by the Japanese govern- the Tokyo Institute of Technology and Toyohashi
and drug discovery. Osaka is renowned for mentsays that approximately 30 percent University of Technology, Japan.
3
OSAK A I N F O CU S: Excellence in Research
T he last half
of the 20th
century saw
Japans
To pull Japan out of the current economic companies as well as the worlds leading government designation as a biomedical industry
malaise, prominent members from academia, research institutes. In recent years, the Northern area in this region, Osaka could act as a catalyst
industry, and government of Osaka Prefecture Osaka Biomedical Cluster has enjoyed a to initiate the spread of ideas for life innovation
the heart of the Kansai region of Western Japan reputation as one of the top biomedical clusters throughout the rest of Japan. Osaka will submit
incorporating the cities of Kyoto, Kobe, and in Japan. a formal application in 2011.
Naraare devising new economic models
based on the historical strengths of the regions Osaka Prefectures Proposal for the The proposal includes:
electronics, chemical, biomedical, and precision Comprehensive Global Strategic (1) Establishment of a PMDA (Pharmaceuticals
instruments sectors. In particular, a strategy that Special Zone and Medical Devices Agency) ofÃce in the
makes full use of Osaka's current expertise in the One of the pillars of the Japanese governments Osaka region to accelerate the development
CREDIT: © OSAKA CONVENTION & TOURISM BUREAU
biomedical, and environment and new energy strategy for economic growth is founded on a of pharmaceuticals and medical devices, and
industries will be the driving force, with a potential vision of so-called Life Innovation for becoming resolve issues related to drug-lag and device-
economic upside of ¥700 billion ($8.3 billion). a leader in research and providing exceptional lag (delays in drug and device development
The history of Osakas biomedical industry health care. Now, Osaka Prefecture will help to and approval due to stringent government
goes back to the 17th century when the realize this national goal by integrating the unique regulations);
Doshomachi district in Osaka City was the potential of Northern Osaka with the world-class (2) Extending the function of the National
national hub for the distribution of herbal biomedical industries and abundance of highly- Cerebral and Cardiovascular Center (NCVC)
medicine and related materials. Centered on skilled employees available in this area. by constructing new buildings to expand the
Doshomachi, the Northern Osaka Biomedical In September 2010, Osaka proposed a draft Research and Development Initiative Center and
Cluster covers an area 40 km in diameter, and of the Comprehensive Global Strategic Special related medical clusters;
includes university startups and pharmaceutical Zone to the national government. With a formal (3) Setting up a Comprehensive Special Zone
4
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by offering consultation, development of human batteries, and develop batteries with Ãve times
resources, and collaborative research; greater energy storage capacity than current
(6) Increasing efforts to attract new vaccine- technology. Future applications include not
related industriesthe growth engines of medi- only automobiles, but also portable devices for
cal industriesto form a strong foundation for improved health care.
the research, development, and manufacture of Taking the lead in the development and
biomedical products. This policy takes advan- adoption of new energy technologies, Osaka
Panasonic's In-Hospital Delivery
tage of Osaka Universitys research institutes will be hosting the Osaka New Energy Forum
Robot, "HOSPI"
the Immunology Frontier Research Center, the 2011, scheduled for 2426 March, at the
Research Institute for Microbial Diseases, and Osaka International Convention Center. Chaired
the Institute for Protein Researchand the Na- by Osaka Governor Toru Hashimoto, the theme
MORE INFO
tional Institute of Biomedical Innovation (NIBIO), of the conference will be to review the role
The Osaka New Energy Forum
located in the Saito Life Science Park, all world of electric vehicles in society. The organizers www2.convention.co.jp/oneforum/en/
leaders in vaccine research. expect about 10,000 participants at the event.
5
OSAK A I N F O CU S: Excellence in Research
edge research from the laboratory to the clinic, and into the home.
Swedish Academy of Science to Kishimoto on clarifying the mechanisms governing the onset education courses for patients and the general
public were initiated on these same therapies.
At the heart center, established in 2007,
clinicians treat severe heart failure and
intravascular disorders as well as perform heart
surgery. We are also developing advanced
medical treatments for cancer and for partial
organ transplants, says Fukuzawa.
The hospital collaborates with internal
Robotic Arm Operated by research groups including the Medical Center
Osaka University Medical School Electrocorticogram for Translational Research (MTR), set up in
6
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2002 to conduct research on topics including division is unique in Japan, says Ohashi. Our
regenerative medicine, robotic surgery, and students have backgrounds in nursing sci-
diagnostic imaging. ence and medical technology science. They are
Being located within the hospital enables us to studying in one of our three unique interdisciplin-
have Ãrst-hand interaction with the patients and ary programs, which are based on informatics,
clinicians, says Toshiki Yoshimine, director of mechanics, and life sciences.
the MTR. Patient conÃdentiality and protection is Yuko Ohno and Kenji Yamada are in
a top priority. Out of an abundance of caution the Department of Robotics and Design for
we have established an ethics committee with Innovative Healthcare. This department reÄects
Kenji Yamada and Yuko Ohno
whom we consult on decisions about exploratory a collaboration between Osaka University and the
clinical trials, says Yoshimine. robotics center at Panasonic Corporation, says
Innovative work is being done in tissue regen- Ohno. Our nurses are working with robotics
eration using a patients own cells. Examples experts to develop a database of how robots
include the use of myoblast sheets produced could operate in hospitals. One exciting project
from femoral muscle for the treatment of cardio- being conducted at the Osaka University, in
myopathy and engineered cell sheets composed collaboration with other groups, is looking at
of oral mucosal epithelium for corneal recon- the potential of robotic beds, which will enable
struction. With this technology there is no risk of patients to move from the bed to a wheelchair
immunological rejection, says MTR Vice Director without human assistance. This is a unique
Akira Myoui. experiment fusing engineering and nursing, says Osaka University Hospital
One of our most challenging projects is on the Yamada. Also, working directly with industry will
brain-machine interface, says Yoshimine. We enable rapid translation to actual applications in aged 65 to 100 to clarify the effects of genetics
are developing technologies to gauge human the future. and environment on health, says Hayakawa.
intent based only on brain activity as an alterna- Immunology is another strong area of research For example, why would one twin die at 70 and
tive means of communication for people with at the Division of Health Sciences led by Haruo the other at 100?
severe motor impairments, such as ALS [Amyo- Sugiyama, developer of the WT1 (Wilms Tumor The twin research project, which is one of
trophic Lateral Sclerosis]. In recent trials, clinical Gene 1) peptide cancer vaccine. We completed the Japanese governments Life Innovation
researchers implanted electrodes directly onto phase one clinical trials at Osaka University programs, will assess 1,000 twins separated in
the surface of the brains of patients with epilepsy Hospital in 2002, says Sugiyama. We are their youth who went on to live in different envi-
or intractable pain in an attempt to treat these now pursuing phase 2 trials. The WT1 gene is ronments. Researchers will use NMR, PET, and
diseases. Analysis of information-based brain highly expressed in both hematopoietic and solid other similar methods to examine the subjects.
responses to simple grasp, pinch, and release tumors. Sugiyama demonstrated that WT1 plays Results will be stored in a biobank accessible to
hand movements in these patients has enabled an oncogenic role via its antiapoptotic function scientists worldwide. We want to use the results
them to control robots in real time. These and promotion of cell motility, and is thus a prom- for preventative medicine, and perhaps even for
are very promising results, says Yoshimine. ising target for cancer therapy. anti-aging strategies, says Hayakawa.
Ultimately we want to develop a commercial, The third major new program at the Division of
fully-wireless implantable system. Health Sciences is the Center for Twin Research,
Kazutomo Ohashi is head of the Division led by Kazuo Hayakawa. This is the Ãrst center
of Health Sciences at the Medical School. Our in Japan to focus on collecting data from twins MORE INFO
Osaka University Graduate School
of Medicine
www.med.osaka-u.ac.jp/index-e.html
7
OSAK A I N F O CU S: Excellence in Research
8
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Clarifying the mechanisms of the innate immune response is important for the
development of strategies for the treatment and prevention of malaria.
9
OSAK A I N F O CU S: Excellence in Research
10
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Preventative medicine not only prevents the spread of disease but also reduces
the cost of national health care budgets.
being used to manufacture CAM70 for export. new production plant. In addition to the manu- humans. These endogenous viruses are so
Ueda admits that, despite the success of facture of vaccines, BIKEN also offers JICA train- called because they become integrated into the
CAM70, Japan still has not eliminated measles ing courses on infectious disease-related topics genome of their host. About eight percent of
due to a lack of complete acceptance of vac- approved by the World Health Organization. the human genome is known to be composed of
cines by young mothers. In the 1990s, BIKEN Plans for the future include a major effort to endogenous viruses, says Tomonaga. But this
transferred the know-how for the production of develop a malaria vaccine. About 40 percent of discovery was a case of serendipity.
chickenpox vaccines to the U.S. company Merck the worlds population lives in malaria-endemic Bornaviruses cause neurological disorders in
& Co., Inc. Our vaccines have had a dramatic regions, says Ueda. We have initiated clinical horses. The name originates from the city of Bor-
effect on reducing chickenpox in the USA, says trials in Uganda for a malaria vaccine based on na in Germany, where outbreaks of the disease
Ueda. Preventative medicine not only prevents the serine repeat antigen [SERA], a protein pro- were recorded to have occurred in 1885.
the spread of disease but also reduces the cost duced by the Plasmodium falciparum parasite, These Ãndings imply that RNA viruses are
of national health care budgets. For BIKEN the which is responsible for malaria. Phase 1 trials extremely old, with analysis suggesting that
patent royalties from the vaccine for chickenpox on vaccine safety were completed in December bornaviruses have coexisted with primates for
raised about ¥10 billion ($120 million) over ten 2010. Malaria is present only in the jungles of about 40 million years.
years, which was used to fund construction of a Asia, but is everywhere in Africa, says Ueda. This report generated a lot of international
About one million people die annually due to news coverage, says Tomonaga. In addition to
Bornavirus brain malaria alone. RIMD researchers are ad- newspaper reporters, the American Museum of
ministrating the SE36 SERA vaccine in Uganda. Natural History contacted us about this discov-
If approval is obtained, the vaccine will be manu- ery, and there is now a panel on display about
factured at the Kanonji Institute of BIKEN, which so-called fossil viruses at the museum.
complies with strict international good manufac-
turing practice (GMP) standards.
In a new initiative, BIKEN is funding a chair
at RIMD to conduct research on dengue fever MORE INFO
starting in April 2011, and will be building a Research Institute for Microbial
Diseases (RIMD)
laboratory at MOCID. www.biken.osaka-u.ac.jp/e/
A recent highlight of research at RIMD is
Research Foundation for Microbial
the discovery by Keizo Tomonaga and col- Diseases of Osaka University (BIKEN)
leagues of DNA remnants of the nonretroviral www.biken.or.jp/english/index.html
bornavirus in mammalian genomes, including
11
OSAK A I N F O CU S: Excellence in Research
of bridging the gap between basic research on drug discovery and drug development for commercialization.
N
IBIO was set up by the Japa-
nese government in April 2005
to act as a mediator between
basic research at universities Koichi Yamanishi Tetsuji Naka
and commercialization by industrial corpora-
tions, says Koichi Yamanishi, director general In April 2010, NIBIO started its second phase center is the only comprehensive research facility
of The National Institute of Biomedical Innovation of research (scheduled for completion in 2014) in Japan conducting research on the cultivation
(NIBIO). Our institute plays a unique role in the focusing on three areas: and biochemical analysis of medicinal plants,
development of drugs in this country. (1) Next generation vaccines with an emphasis says Kawahara.
The institutes three main functions are on the development and understanding of adju- The center cultivates and preserves more
conducting basic research, sharing biological vants to enhance efÃcacy; than 4,000 species and groups of medicinal
resources, and funding research. Furthermore, (2) Drug toxicity testing systems including a plants, and supplies seeds and advice to other
NIBIOs Tsukuba Primate Research Center hous- new method to induce differentiation in a variety research institutes. Notably, only 12 percent of
es a large scale breeding colony of about 2,000 of stem cell types; the medicinal plants used in Japan are produced
monkeysmostly cynomolgus macaques (3) Treatment of intractable or rare diseases by in the countrythe remainder being imported
whose family history has been recorded for over analyzing the molecular mechanisms governing from China and other countries. We want to
30 years, making it a valuable resource available these disorders and the development of relevant expand the sources of these second type of
to researchers in pharmaceuticals research and technologies for diagnosis and treatment. rare-earthsthe Ãrst kind being metals such as
development. Since 2008, NIBIO has been working on two lithium used in batteriesby working with other
NIBIOs budget for Ãscal 2010 is ¥11.20 billion industry-academia-government collaborative countries, says Kawahara.
($133 million). We actively support innovative projects based on Super Special Consortia Recently, a research group at RCMPR
ideas, says Yamanishi. It is not widely known programs for the development of cutting-edge produced liquorice root by hydroponic culture
that NIBIO funded Shinya Yamanaka during the medical care. They are the Next Generation growing plants using mineral nutrient solutions
early stages of his research on induced pluripo- Infectious Disease Vaccine Innovation Program, in water and without soil. Liquorice root contains
tent stem (iPS) cells. NIBIO also funds venture and the Development of a Novel Drug Toxicity the sweet-tasting compound glycyrrhizin and is
companies and offers grants and consultation Testing System using human iPS cells. Notably, widely used as an herbal medicine, as well as a
on so-called orphan productspharmaceuticals these projects were two of only 24 such sweetener for food products.
and medical devices for rare diseaseswhich programs approved by the government. Furthermore, another medicinal plants group
large corporations can be reluctant to invest in The development of a drug takes about 15 has developed medicinal treatment for Leishma-
because of the small numbers of affected pa- to 20 years, says Yamanishi. NIBIO was set up niasis, a disÃguring disease transmitted by sand
tients and consequently limitations in recouping only Ãve years ago, and during the second phase Äies, based on screening of medicinal plants
development costs. of research I want to push for actual commer- in countries including Myanmar, Peru, and the
In spite of the relatively small size of NIBIO, cialization of some of the drugs being studied in Solomon Islands. We used the local
statistics underscore the signiÃcant scientiÃc con- our projects. NIBIO also works with inter- knowledge to produce a solu-
tributions of its 50 full-time researchers and their national groups including Cambridge tion for this disease, says
groups. For example, in Ãscal year 2008 each University (on bioinformatics), as well Kawahara.
NIBIO researcher received on average ¥16 million as Peru and the Solomon Islands
($190,000) from competitive grantsthe highest (on medicinal plants). SOCS for Intrac-
grants per person ratio for researchers at Japans table Diseases
approximately 30 independent administration Medicinal Plant Research Tetsuji Naka is the
agencies. Furthermore, in 2009 each researcher Nobuo Kawahara is director of project leader of the Im-
published an average of three peer-reviewed the Research Center for Medicinal mune Signaling Project.
papersabout twice the number in 2005. Plant Resources (RCMPR). Our We need to work on
12
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We hope that our research will enable a reduction in both time and cost of drug
development, as well as the development of safer drugs.
people, says Naka, and not [only on] cells or 150 drugs. The database can be applied in the
lab animals. So we are working with colleagues early stages of drug development to predict
at the Osaka University Graduate School of toxicity risk and characterize the molecular
Medicine on the treatment of intractable diseases mechanism of this toxicity, without the need for
such as cancer using SOCS [suppressor of expensive animals testing.
cytokine signaling] gene delivery. We hope that our research will enable a
SOCS is a family of genes involved in inhibiting reduction in both time and cost of drug develop- Treatment of malignant pleural mesothelioma
the Janus Kinase/Signal Transducer and ment, as well as the development of safer drugs,
Activator of Transcription (JAK/STAT) signaling says Urushidani.
pathway. Abnormal expression of SOCS
molecules can cause dysregulated cytokine Vaccines and Innovative Adjuvants
signaling, which leads to the development of Ken Ishii is the project leader of the Laboratory
disease, says Naka. for Adjuvant Innovation. He is developing vac-
Recently, Naka and colleagues found over- cines and their adjuvantssubstances added to
expression of SOCS3 in cancer cells to be an vaccines to increase the response of the immune
effective new treatment for malignant pleural system. Ishii joined NIBIO because he wanted to
mesotheliomaa form of lung cancer caused take his ideas from the lab to real world applica-
by exposure to asbestos. This is an important tions, and not just write high-impact papers.
development considering that asbestos-related We lack a fundamental understanding of the
diseases are expected to reach a peak in mechanisms by which viral preparations affect
around 2030. the immune response of the body, says Ishii. In
October 2010, we established the Next Genera-
Predicting the Toxicity of Drugs tion Adjuvant Research Group to address these
Tetsuro Urushidani is project leader of the issues. Notably, the Adjuvant Group includes
Toxicogenomics/Informatics Project, which was members from vaccine manufacturers and ven-
recently awarded The Presidents Prize from the ture capital companies.
Science Council of Japan for the development of Recently, Ishii reported on why some inÄuenza
new biomarkers for human safety. This is a large vaccines work better than others, and deter-
project involving academia, government, and 13 mined that a rare immune system cell type,
companies, including Astellas Pharma, Daiichi plasmacytoid dendritic cells, modulate the effect Hierarchical clustering of genes and chemicals
Sankyo, and Takeda Pharmaceutical Company, of inactivated Äu virus vaccines, but not live virus
says Urushidani. vaccines. These results highlight the importance
The project has yielded a toxicology database, of our research, says Ishii. We need a scientiÃc
called the Toxicogenomics Project-Genomics approach to understanding adjuvants, otherwise
Assisted Toxicity Evaluation system (or TG- interest in adjuvant research may dwindle, similar MORE INFO
National Institute of Biomedical
GATEs), containing millions of data points to the demise of gene therapy with viral vectors,
Innovation
collected by observing in vitro changes in gene which saw a dramatic decrease in activity follow- www.nibio.go.jp/english
expression following administration of more than ing the death of patients on this therapy.
13
OSAK A I N F O CU S: Excellence in Research Advertisement
MORE INFO
National Cerebral and Cardiovascular
Center
www.ncvc.go.jp/english/
Haruko Yamamoto Yoshihiro Miyamoto Takeshi Nakatani
14
Advertisement OSAK A I N F O CU S: Integrating Research and Business
T he Northern
Osaka
Biomedical
Cluster
consists of an area covering
a 20 km radius, centered
The cluster was established based on the Institute of Advanced Industrial Science and called the Osaka Bio Strategy has been laid
ambitious vision of Yuichi Yamamura, former Technology (AIST). out. These goalsincluding that the Osaka
president of Osaka University, to make Northern In the cluster, the Saito Life Science Park Bio Cluster should rank at least 5th worldwide
Osaka a destination for the life sciences. (LSP) is becoming increasingly important as a in the biomedical Ãeld within 10 yearswere
This vision is now coming to fruition. A sig- place to conduct biotechnology research and devised by the Osaka Bio Strategic Promotion
niÃcant development was the opening in Sep- business, with 40 companies and approximate- Conference, headed by Toru Hashimoto,
tember 2008 of the Osaka Bio Headquarters at ly 1,300 researchers and support staff working governor of Osaka, and chaired by Tadamitsu
the Senri Life Science Center building to act as on site. Small and medium sized companies Kishimoto, former president of Osaka University.
a bridge in coordinating bioscience projects in- and university startups will be able to expand The Osaka Bio Strategic Promotion Confer-
volving academic, industrial, and governmental their business at the Saito Bio Incubation ence consists of 10 organizations (listed on
organizations. Additionally, a number of startup Facilities, which include wet labs and animal page xv). The policies of the Conference are
companies have been established in the area, research facilities. implemented by the Osaka Bio Support Group,
over 300 Osaka Pharmaceutical Manufactur- Additionally, a new industrial park neighboring made up of 20 members from the front line
ers Association (OPMA) member companies the Saito LSP is scheduled to begin operation in of the biotechnology Ãeld, led by Isao Teshi-
are conducting business around Doshomachi, the spring of 2014. It is expected that innovative rogi, president and representative director of
and world-class research is being carried out industries, including those in the life sciences, Shionogi & Co., Ltd.
at institutes such as the National Institute of will move to this area and join those already In an effort to support startup companies,
Biomedical Innovation, the National Cerebral established in the Saito LSP. the Osaka Bio Strategy made provisions for
and Cardiovascular Center, Osaka University, To accelerate biotechnology development the Osaka Bio Fund¥1.1 billion ($13 million) in
Osaka Prefecture University, and the National in the Osaka region, an ambitious set of goals assets to provide Ãnance for new continued »
15
OSAK A I N F O CU S: Integrating Research and Business
World Medical Polis, Osaka Booth at MD&M in Institut Pasteur has signed an
Minnesota Event in Osaka Minneapolis MOU with OCCI
ventures in pharmaceutical products and medi- tionally, having organized successful meet-
cal devices. ings for European and Korean companies on
Osaka Bio Strategic Making the most of another of Osakas Alzheimers disease.
advantagesa highly-skilled biotech workforce The Medical Device Forum holds regular
Promotion Conference
from world-class universitiesOsaka Bio Head- monthly meetings where professional
Member Organizations quarters provides human resources matching medical researchers and doctors from
programs to introduce postdoctoral research- medical institutions propose joint projects for
Ministry of Economy, Trade ers and senior specialists to startup companies. industry to develop, such as medical devices,
On the clinical side, Osaka Bio Headquarters biomedical protocols, and equipment. OCCI
and Industry (METI), Kansai
organizes the Osaka Clinical Trials website in conducts the World Forum for BIO/MEDICAL
Bureau
cooperation with OPMA. The website releases Device in Kansai for stimulating alliances
the results of clinical trials run by Osakas 13 between Japanese and overseas companies
National Cerebral and highly specialized hospitals. in medical device Ãelds. Utilizing the Kansai
Cardiovascular Center Established in May 2009, the Protein Mall region's strengths in developing advanced
Kansai (PMK, protein-mall.osaka-bio.jp/en/) medical platforms, these initiatives are seen
National Institute of is Japans largest assembly of protein-related as economic models that can be applied
Biomedical Innovation research institutes and companies, organized nationwide in the drug discovery and the
by the Osaka Bio Headquarters and the Senri medical device industries.
Osaka Bioscience Institute Life Science Foundation.
The 75 members of PMK aim to create International Partnerships
Osaka Chamber of Commerce commercial opportunities through the practi- In February 2010, OCCI signed a memorandum
cal application of protein-related research, of understanding (MOU) with the Bio Business
and Industry
the promotion of collaborative research, and Alliance of Minnesota, United Statesone of
the support of contract research, all of which the top medical device clusters in the world
Osaka Pharmaceutical
contribute to innovative technology and new with the goal of forming an alliance between
Manufacturers Association business in the Kansai region, which includes Japanese and Minnesota-based companies to
Osaka and Ãve other Prefectures. promote the development and commercializa-
Osaka Prefectural Government The Osaka Chamber of Commerce and tion of medical devices.
Industry (OCCI) promotes open innovation by Furthermore, an MOU between OCCI and In-
Osaka Prefecture University providing business-matching programs. Spe- stitut Pasteur in Paris, France in the Ãeld of drug
ciÃc programs include the Drug Seeds Alliance development was signed June 2010. Institut
Osaka University Network Japan (DSANJ, www.dsanj.jp/e/) with Pasteur maintains a presence on the DSANJ
OPMA as a co-organizer, formed to accelerate database, posting technology information that
Senri Life Science Foundation technology transfer in the following areas: drug serves to promote alliances with Japanese
candidates and targets; foods and cosmetics; pharmaceutical companies.
biomarkers, diagnostics, and reagents; and The Kansai Bio Promotion Conference has
platform technologies. also signed MOUs with partners in France, Bel-
OCCI maintains the DSANJ database and gium, and the State of Queensland in Australia.
conducts partnering events categorized by dis- These alliances are possible because of the
ease area, country, or region. There are already historical accomplishments of the life sciences
164 organizations networked as technology community in Osaka. This community plans to
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providers, and 55 pharmaceutical companies continue building upon this strong foundation,
Osaka Bio Headquarters
www.osaka-bio.jp/en/ with a presence in Japan have registered as creating greater potential for life science-related
technology searchers. DSANJ is active interna- research and business in the future.
16
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I
n the early days this institute was
addressing issues related to nutrition,
says Toshiharu Hase, director of the
Institute for Protein Research (IPR). Now
Toshiharu Hase Junichi Takagi
we conduct fundamental research on protein
scienceP450 was discovered here. We also clariÃed the 3D structure governing semaphorin Malfunction of homologous recombination
support the development of the Worldwide signaling through the plexin receptor. We used leads to cancer and infertility in humans, says
Protein Database and the Protein Data Bank of X-ray analysis to determine the 3D structure of Shinohara. My research interests are to clarify
Japan [PDBj, www.pdbj.org]. Semaphorin 6A and Plexin A2, before and after the mechanism of homologous recombination
The IPR has state-of-the-art research signal transmission, says Takagi. Our discovery in eukaryotes and the mechanism of meiotic
facilities, including equipment for X-ray analysis will contribute to the understanding of the recombination.
and a powerful 950 MHz nuclear magnetic mechanism underlying many serious diseases Shinohara is studying the role of protein/genes
resonance spectrometer. There are also plans and the development of new drugs. Indeed, in the RAD52 family both in vivo and in vitro, and
to install a cryo-electron microscope. Notably, this report resolves the structural mechanism in particular, researching Rad51a homolog of
IPR has a dedicated beamline at the SPring-8 governing receptor activation, namely the bacterial RecA. Notably, Rad51/RecA is known
synchrotron facility in Hyogo, which is available transmission of signals across membranes. to form a right-handed helical Ãlament on single-
for collaborative research. Takagi is also conducting research on stranded (ss) DNA and carry out homology
IPR has inter-faculty agreements with a number the structure of proteins that are implicated search and strand exchange during the recom-
of academic institutions, including Peking in neuronal synapse functions through bination process. Since the Rad51-mediated
University in China, Yonsei University and Seoul ultrastructural analysis of proteins using electron exchange event is inefÃcient in vitro, other factors
National University in South Korea, National microscopy and tomography. must be required to promote this reaction, includ-
Tsing Hua University in Taiwan, Indian Institute of I want to use our know-how to tell the whole ing Rad52-mediated formation of a ring-like
Chemical Biology in India, and the University of biological story based on the 3D structures of structure on the ssDNA, which facilitates the
Manchester in the United Kingdom. The institute proteins, says Takagi. binding of Rad51 to the DNA.
also often welcomes international scientists, for Also interested in structural biology is Akira We are also studying recombination and
example it hosted eight researchers from seven Shinohara at the Laboratory of Genome and chromosome dynamics during meiosisa type
overseas countries in 2009. Chromosome Functions, who is investigating of cell division that occurs during the production
IPR is also the source of new, enabling the molecular mechanisms of homologous of gametes [eggs and sperm], says Shinohara.
technologies. Junichi Takagi is a structural recombination using molecular, genetic, and Recent work has implicated the Csm4 protein
biologist at the Laboratory of Protein Synthesis biochemical methods. in the speciÃc movement of DNA ends during
and Expression. Our group recombination. Our results imply that chromo-
has developed a high some movement promotes a variety of biochemi-
purity recombinant protein cal reactions on chromosomes including meiotic
expression/puriÃcation recombination, says Shinohara. More recent
system for a wide range of experiments indicate that physical forces may be
proteins, says Takagi. We regulating chromosome functionsthat is, phys-
have created an inexpensive ics may regulate biochemistry.
and fast afÃnity puriÃcation
method, which has played a
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vital role in many structural
Institute for Protein Research,
biology projects. Recently, Osaka University
Takagi was the focus of www.protein.osaka-u.ac.jp
international attention when he Akira Shinohara
17
OSAK A I N F O CU S: Integrating Research and Business
which are open to overseas participantsand In 2011 and 2012, Yanagida is launching two tion installed information network (BFI).
supports collaborative visits of students and major interdisciplinary The aim of these collabora-
postdocs to universities and research institutes projects. One is the tions is to analyze the Äow of
in the United States, Europe, and Asia. Quantitative and information, energy, and materi-
Namba is a biophysicist specializing in Computational Biology als within living organisms and
biological nanomachines. We analyze the Center (QBiC), which interface them with an external
structure and dynamics of macromolecular begins in April 2011 control system. We will start
assemblies using techniques including electron and aims to develop with single molecules and work
a comprehensive up towards the whole brain,
understanding of explains Yanagida. Ultimately,
MORE INFO biological system such studies are expected to
Graduate School of Frontier Biosciences, dynamics. This is a lead to the construction of highly
Osaka University
www.fbs.osaka-u.ac.jp multi-institute project energy-efÃcient machines and
with Osaka University Toshio Yanagida advanced medical diagnostics.
18
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a range of pharmaceutical and health sciences, including cancer and psychiatric disorders. Here, we talk to two prominent
19
OSAK A I N F O CU S: Integrating Research and Business
W
hat is a dentist? asks
Toshiyuki Yoneda,
dean of the Graduate
School of Dentistry at
Osaka University. I am afraid that dentistry is
Graduate School Approach for Periodontal
still viewed as a surgical-based vocation involv- of Dentistry Tissue Regeneration
ing Ãlling cavities and pulling teeth. We want to
destroy this antiquated view because we believe introduction of special lectures on biodentistry, results showing that teeth weakened by
that the future skill sets of dentists must cross creation of a personal genome database using periodontal problems can be made stronger by
many disciplines, including pharmacology, law, oral bioinformatics, and the establishment of an drug therapy using Ãbroblast growth factor-2
and even the arts. intractable diseases international station. [FGF-2].
The heart of the problem in Japan is the rap- In addition to these plans, Yoneda and his At the Cell Processing Center, the group led by
idly aging population. The majority of patients in colleagues are also involved in cutting-edge Shinya Murakami, head of the Department of
Japan are middle-aged or above, and traditional research. Recent highlights include studies Periodontology, is extracting fat cells to generate
ailments such as tooth decay are no longer the on bone biology in which the researchers periodontal tissue. This is the Ãrst such center
main issues for dentists, says Yoneda. For ex- discovered a link between stress signals in in a dental school in Japan and, although we are
ample, periodontal disease in an elderly patient the endoplasmic reticulum (ER)an important still in the early stages, we have had encouraging
can be linked to other diseases such as diabetes cellular compartment in which protein folding results that indicate the possibility of producing
and cardiovascular disease, so dentists must be occursand activation of vesicular trafÃcking periodontal tissue from fat cells, says Yoneda.
able to understand these other systemic disor- out of the ER. The Osaka University Graduate School
ders. We must revise the education curricula for In an equally high-impact contribution, of Dentistry holds many joint symposia with
dental schools to include a deeper understand- Yonedas group conducted experiments in an universities and institutes in the United States,
ing of molecular biology and pathophysiology. attempt to quantify pain. Pain is a subjective United Kingdom, Korea, and Thailand. Osaka
Yoneda also says that he wants Osaka experience, but our experiments show promise students can go to the United States for two
Universitya comprehensive university with as a means of producing an objective view, says month home stays to improve their English.
schools of medicine, pure sciences, engineering, Yoneda. Experiments on inÄammatory pain in The dental school holds regular community
and artsto introduce new curricula for training rats showed the importance of proton sensing outreach forums to emphasize the importance
dentists. As a Ãrst step, Yoneda has submitted receptors, such as TRPV1, in the transmission of of dentistry, and its evolution, for the young
a proposal to the Ministry of Education, Culture, pain. When activated, and old.
Sports, Science and Technology to establish a TRPV1 appears to Surgery at the Translational Osaka University was
program on Life Innovation. The six-year pro- upregulate calcitonin Research Center the Ãrst government-
gram would focus on intractable diseases of the gene-related peptide run comprehensive
mouth and their relationship with other diseases (CGRP) expression, a university to establish a
of the body. Distinctive features of the program scenario associated school of dentistry. We
include: the awarding of a Master of Oral Dis- with inÄammatory pioneered dentistry in
eases to graduates of a post-residence course, pain. Japan, says Yoneda.
We have also been I am conÃdent that our
working on using new initiatives based
drugs to treat oral on a molecular biology
MORE INFO
diseases, instead of approach will inspire
Graduate School of Dentistry,
Osaka University
periodontal surgery, education and research
www.dent.osaka-u.ac.jp/english says Yoneda. We at dental schools in
have convincing Japan and globally.
20
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creating a new system biological ¿eld of life sciences that predicts biological function through atomic-level analysis.
I
n spite of the tremendous advances in The four aspects required for understanding
the life sciences, it is still not possible to the whole cell system are: (1) structural
accurately predict the results of medical genomics, (2) functional genomics, (3) functional
treatment, says Seiki Kuramitsu, analysis of each system, and (4) simulation and
professor in the Department of Biological prediction of all biological phenomena in the cell.
Sciences, Graduate School of Science, Osaka The goal of our so-called Whole Cell Project
University. This department was established in is prediction, as opposed to explanation, says
1949 for education and research in the biological Kuramitsu. I want to move from molecular
sciences, based on advances in science at the biology to atomic resolution biology.
boundary of chemistry and physics. I believe This is a human project, not just an Osaka
that it is necessary to construct a new Ãeld of life Seiki Kuramitsu project, adds Kuramitsu. Also, this is not a
science whereby we can predict the response of subject just for medical school researchers; it
an organism based on chemistry. Thermus thermophilus HB8, an extremely is an interdisciplinary subject. We welcome the
Kuramitsu's laboratory and many research thermophilic bacterium that thrives at 80ºC, is worlds scientists to join us.
groups are investigating whether biological an excellent model for structural and functional
phenomena underlying different environmental studies. Its constituent proteins are stable,
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stimuli can be deÃned in single cells by and most of its approximately 2,200 genes are
The Whole Cell Project
studying the 3D structure and function of all common to many other organisms, including www.thermus.org/e_index.htm
the intracellular molecules at an atomic level. humans, says Kuramitsu.
program was launched in 2009, says Hiroshi Ishiguro. The big question is whether Osaka
We welcome doctoral candidates
Ishiguro, leader of the program. I believe that University can do this.
we were awarded the project because of our The research and educational activities of the from overseas to join us to create
interdisciplinary approach towards cognitive GCOE program are coordinated with the Ad- human-friendly robots based on
science and robotics. vanced Telecommunications Research Institute
The project involves experts from robotics, International (in Kyoto) and the National Institute cognitive neuroscience.
neuroscience, and human sciences. Cogni- of Information and Communications Technol-
tive neuroscience is related to meta-level brain ogy (in Hyogo) in Japan, and institutes overseas
functions such as memory and reasoning, says including the Italian Institute of Technology and
Ishiguro. Conventional information and robot Bielefeld University in Germany. MORE INFO
technology, IRT, has produced a more conve- We welcome doctoral candidates from Global COE Program Center of
nient world but without regard for effects on our overseas to join us to create human-friendly Human-friendly Robotics Based
on Cognitive Neuroscience
cognitive functions. We want to establish new robots based on cognitive neuroscience, www.gcoe-cnr.osaka-u.ac.jp/english/
paradigms based on cognitive neuroscience for says Ishiguro.
21
OSAK A I N F O CU S: Integrating Research and Business
MORE INFO
National Institute of Advanced Industrial
Science and Technology (AIST), Kansai
www.aist.go.jp/index_en.html
22
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development of a similar treatment in humans. Using dendritic cells (DC) developed from peripheral
es at three campuses: Nakamozu, Habikino, Ikuo Fujii, based at the Graduate School of blood monocytes (Mo) by granulocyte-macrophage
and Rinku. Science, is an active member of the Osaka Pre- colony stimulating factor (GM-CSF) and interleukin
Here, we introduce the research activities of fecture Bio Strategy Committee and is commit- (IL)-4, DC-based immunotherapy has provoked
Ãve members of the OPU faculty who are actively ted to making Osaka a center for life sciences. immune responses against cancer in human
involved in the Osaka Prefecture University Bio Fujii has recreated in the laboratory the process patients. However, improvements are necessary
Strategy Committee on the development of bio- by which the immune system makes antibodies in order for the immune response to be sufÃcient
industries in the Osaka Bay area. and is developing low molecular weight peptides for a satisfactory clinical outcome. Interferon-
Kikuya Sugiura, a veterinarian at the School known as microantibodies. This will allow him to gamma (IFNγ), a potent inducer for DC maturation
of Life and Environmental Sciences explains his contribute to moleculartargeted medicine and and T helper type 1 response, is an important tool
research: I am developing immunology-based advanced medical diagnostics, says Fujii. for achieving such improvements. Inoculation of
therapy for tumors using dendritic cells [DC]. In particular, Fujii is addressing problems asso- canine IFNγ with DC into the microenvironment of
The function of DC is to present antigens to T ciated with antibody medicine. These problems canine tumors signiÃcantly improved the clinical
lymphocytes, activating the immune response. include antigenicity, manufacturing costs, and outcome, including complete remission of mammary
We are obtaining these cells in culture by induc- cell membrane permeability issues. I am repro- carcinomas. For obtaining local-limiting and long-
ing the differentiation of monocytes isolated from ducing the functions of antibodies using small lasting effects of IFNγ, methods are being developed
blood, which can then be used to Ãght cancers. peptides, says Fujii. I have developed a unique for in vivo transfection of the canine IFNγ gene into
This method alone, however, is not effective phage-display peptide library of peptide sur- tumor cells using a gene delivery system (GDS).
in completely destroying tumors. In a novel faces, which are stable against proteases in the Results from the study of dogs with common human
approach, Sugiura injects interferon γ (IFNγ)a blood, show high binding activity and speciÃcity, tumor types may provide useful information for the
potent inducer of the T lymphocyte-mediated and are highly membrane permeable. These development of human cancer therapies.
immune responsealong with DC into dogs exciting results are expected to
with naturally occurring tumors, brought to contribute to the development of the MRI-detectable dendron
thermosensitive polymer
the OPU veterinary school for cancer therapy. next generation of antibody-based biocompatible polymer
This treatment induced complete healing in the therapeutics and diagnostics for the
dogs, says Sugiura. They are an almost perfect detection and treatment of cancer.
model for these experiments because breast The precise and reproducible
cancer, lymphoma, and osteosarcoma occur delivery of bioactive molecules
spontaneously. So if the treatment is effective in to speciÃc targets is essential
dogs, there is a very high probability that it will for the development of medical
work in humans. treatment protocols. Chemist Kenji Detection of liposome
accumulation with MRI
Sugiura is also testing drug delivery directly Kono is developing biofunctional
into the tumor microenvironment by introducing nanomaterials for the delivery
cytokine genes into tumor cells using a gene of drugs to treat cancer. The
delivery system. Applying IFNγ and DC together development of accurate drug
appears to create a strong synergistic immune delivery technology is critical for
response against tumors, providing hope for the personalized chemotherapy, continued » Detection of liposome accumulation of mouse tumor with MRI
23
OSAK A I N F O CU S: Integrating Research and Business Advertisement
We are aiming to lead research in the ¿eld of high-precision, liposome- and
dendrimer-based drug delivery.
24
OSAK A I N F O CU S