Application for Academy Center Certification
World Premier International Research Center Initiative (WPI)
Host Institution

Tokai National Higher Education and Research System, Nagoya University

Research Center

Institute of Transformative Bio-Molecules

Host Institution Head

Seiichi Matsuo

Center Director

Takashi Yoshimura

Administrative Director

Tsuyoshi Matsumoto

Please prepare this application based on the content of your Center’s progress report and the progress plan you submitted for the Center’s
final evaluation. Summarize the Center’s future plans with regard to the following 8 items within five A-4 pages. (Also fill out the
appendices at the end of this form.)

1. Overall Image of Your Center* Describe the Center’s overall image including its identity.

ITbM is an international research institute established at Nagoya University (NU) to develop“transformative bio-molecules” that make a marked change in the form and nature of biological scienceand technology. ITbM gathers world-leading researchers in the fields of synthetic chemistry, biology,
and theoretical science and they work together to conduct interdisciplinary research. ITbM establishedthe Mix Lab and Mix Office where researchers and students from different fields are sitting side-byside and naturally have discussions based on a flat relationship irrespective of their titles. ITbM
implements measures to promote bottom-up collaboration, such as the ITbM Research Award. ITbM
also starts "Chalk Talk" which provides opportunities for researchers to present their unique ideas.
ITbM extends its global network to further advance its interdisciplinary research via extensive collaboration.
With the cutting-edge research outcomes, ITbM is now widely recognized as an international research hubof chem-bio research. ITbM is positioned as a flagship research institute in NU, and has been inducing
system reforms of NU. In 2018, a new graduate program “Graduate Program of Transformative Chem-Bio
Research (GTR)” was established as a MEXT “Doctoral Program for World-leading Innovative & Smart
Education (WISE)” having ITbM as its core. The Graduate School of Science makes a system reform andofficially allocates PhD students also to ITbM’s overseas PI groups from FY2022. ITbM will work proactively
in nurturing PhD students who can pioneer new science at the interface of multiple disciplines.
ITbM will also actively engage in societal implementation of research results. As represented by thedevelopment of parasitic plant striga eradication molecules, a number of socially implementable
results have emerged regarding environmental adaptation in plants. ITbM will continue and acceleratethese researches. Meanwhile, under the new Director Yoshimura, ITbM implements new research
initiatives that contribute to improving human health, such as overcoming health hazards associatedwith climate change and animal-borne infectious diseases. ITbM launched a membership discussion
forum “ITbM Consortium” in 2017 to provide matching opportunities with industries, which was revamped
in 2020 as “ITbM/GTR Consortium” and incorporated a wider range of researchers who engage in the GTR
program.
ITbM has now become a truly exciting and internationally visible institute where new interdisciplinary
research fields emerge and new molecules are born every day. Meanwhile, we sincerely examined therecent case of the research misconduct, and took measures to ensure to prevent any research
misconduct. We will also take this as an opportunity to further develop our research, and expand
ITbM's unique "Mix" by integrating a wider range of disciplines. ITbM’s unique “Mix” culture has led
researchers from different fields to work together and think/act differently, thereby finding uniqueproblems and solutions, discovering something new, and providing unique solutions to key global problems.

Tokai National Higher Education and Research System, Nagoya University - 1
Institute of Transformative Bio-Molecules2. Mid- to Long-term Research Objectives and Strategies* Describe new challenges in the Center’s research objectives and plans after FY2022.

In April 2022, Dr. Yoshimura assumed the ITbM director’s post. With the slogan of "openness,transparency, and inclusion," ITbM made organizational reforms under the leadership of the new
Director in cooperation with NU to ensure that research misconduct will never occur. ITbM takes thisas a good opportunity for further development of ITbM by expanding interdisciplinary research andenhancing our research capabilities.
The mission of ITbM has been to conduct ‘needs-inspired’ basic research while developing transformative
bio-molecules that make a marked change in the form and nature of biological science and technology. By
marrying state-of-the-art synthetic chemistry, catalytic chemistry, plant biology, animal biology, live
imaging, and theoretical science, ITbM has advanced new research areas of "plant chemical biology","chemical chronobiology", and "chemistry-enabled live imaging". This exciting endeavor has resulted in
the development of a range of promising bio-functional molecules, many of which have beencommercialized, and the discovery of molecular mechanisms of important biological events. All of these
tour-de-force achievements have led scientists in the world to place ITbM as an enabling institute where
new bioactive molecules with targeted properties can be rapidly discovered, designed, and synthesized.
ITbM continues to promote research aimed at the development of transformative biomolecules andto open up new research fields through interdisciplinary collaboration. Whereas advancing the
research on animal/plant science that has been promoted so far, under the initiative of the new
Director, ITbM will work on the research that contributes to human health with a view of the recent
global climate changes. For this purpose, ITbM adds data science as its fourth pillar. Data science will
also make a significant contribution to the research that ITbM has been working on. Keeping in mind
the promotion of diversity, ITbM appointed a new PI and two junior PIs who are necessary to tackle
this research area (see Section 3), and will take on the challenges listed below for the next 5-10 years.
Through their achievement, ITbM will be further recognized as a world-leading research institute.
(1) Parasitic Plants: Based on our discovery of significant potential molecules for combatting theparasitic plant Striga, ITbM will make efforts to provide molecular solutions to the food security issues,
especially focusing on Africa. For this purpose, we have initiated a collaboration with Kenya
Agricultural & Livestock Research Organization (KALRO) and the International Center for Researchand Education (ICREA) of NU. We are confident that our molecular approach can be used to combat
other parasitic plants causing huge damage in other regions.
(2) Chemistry-enabled plant adaptation: Plants have inherent stress tolerance systems thatenable them to adapt to environmental changes and survive under stressful conditions that are
essential functions due to their inability to move. However, recent global climate change exceeds thetolerance of the current abiotic stress response of plants, and they often face serious situations suchas failing to fertilize, failing to develop, and eventual death. We aim to develop such environmental
stress-overcoming molecules to maximize the adaptive power of plants via an interdisciplinary
approach.
(3) Chemistry-enabled bioimaging: Bioimaging is one of the indispensable techniques in current
biology. We have developed a series of new fluorescent dyes. Their outstanding photostability enabledacquiring not only 3-D structures of cytoskeletons, but also mitochondrial inner-membrane dynamics
in the living cells by conducting STED imaging. Near-infrared (NIR) fluorescent dyes are the othertarget molecules in our research, which have several advantages, such as diminishing photo-damage
to bio-samples, minimal interference from cell autofluorescence, and deep penetration in biologicaltissues. With these sophisticated dyes in hand, together with state-of-the-art imaging
instrumentations, we will make full use of these cutting-edge discoveries to understand and control
biological systems, and also contribute to the advancement of medical diagnosis.
(4) Nanocarbon chemistry and biology: While it is important to strengthen fundamental
technologies such as molecular synthesis, it is also important to create molecules with new structuresand clarify their properties in order to maximize the potential of molecules. On the other hand, it isalso important to create molecules with new structures and clarify their properties in order tomaximize their potential. To this end, we will apply molecular nanocarbons as new molecular entities
in biology and explore “nanocarbon biology” as a new scientific field. All the findings will be applied
to other projects at ITbM, adding a new dimension to biological science and technology.
(5) Clock-disease: Disturbances in the circadian system have a profound impact on health, andthey have been linked to several pathologies, including obesity, psychiatric disorders, cardiovascular

Tokai National Higher Education and Research System, Nagoya University - 2
Institute of Transformative Bio-Moleculesdisease, and even cancer. ITbM has developed a number of molecules, such as circadian clock
regulators with anti-cancer properties, that have been shown to reduce jet-lag. The human menstrual
cycle, sleep-wake cycle, and manic-depressive cycle are all influenced by the phases of the moon. In
traditional agriculture, the phases of the moon were also used for planting and harvesting. In the
animal kingdom, lunar phases are widely used for migration, mating, and predator avoidance. Thus,
it is clear that lunar influences are involved in life functions and human health. ITbM tackles to
elucidate the molecular mechanisms of these effects via collaborative approach.
(6) Climate change resilience: Global climatic and environmental changes are exceeding theadaptive capacity of not only plants but also animals including humans. Due to global warming, thenumber of heat stroke patients and deaths is on the rise, and health hazards caused by heat waves
are serious worldwide. In addition, animal-borne infectious diseases such as dengue fever and Zika
fever are on the rise. Heat stress also reduces the reproductive efficiency and growth of livestock,
poultry, fish and shellfish. Using data science, we will elucidate the mechanisms of environmental
adaptation in animals and promote the development of molecules that control environmental
adaptation. We will also contribute to the improvement of human health by tackling animal-borne
infectious diseases such as dengue fever and Zika fever through the power of molecules.
3. Management System of the Research Organization* Describe the system of organizational management via which the center will execute the above-described research strategy and plan.
* In Appendix 1-3, list the Principal Investigators, enter the number of center personnel (researchers, research-support staff, andadministrative staff), and provide a diagram of the Center’s organizational management system.

Prevention of research misconduct: ITbM sincerely examined the recent case of research
misconduct, and took all measures to ensure to prevent any research misconduct. We will also takethis as an opportunity to further develop our research through organizational reforms. ITbM has
operated under a top-down management system from the start, and the Director has the authority to makefinal decisions over all matters concerning the operation and management of ITbM. This approach has
eliminated bureaucratic processes and enabled ITbM to make quick and flexible decisions. On the other
hand, the hierarchical organizational management could have contributed to trigger research misconduct.
Therefore, under the initiative of the new center director, the organization was reformed to a flat
structure with “openness”, “transparency”, and “inclusion” as keywords. While eliminating thebureaucracy, we will foster a culture in which opinions can be exchanged regardless of his/her title. Actually,
all members of ITbM will be addressed as "##-san (e.g., Yoshimura-san)," each other. The
ITbM Steering Committee meeting, which had mostly been led by PIs, was changed to asystem that allows all ITbM faculty members to participate. This change brought about remarkablechanges within just a few months; as they were able to share various issues, young researchers became
more proactive to improve ITbM, and the ITbM’s research activities were significantly revitalized.
Another initiative to prevent research misconduct is a double-mentoring system. The system has
been applied to the students of the WISE program GTR (see Section 2-2). The open educational systemurges students to communicate with a second mentor from other laboratories. Accordingly, the students
naturally tend to consult with their double mentors when they have any problems. This system is also
effective to create new collaborative research via scientific talks with the second mentor. We also strongly
encourage students to study abroad by all means such as the travel support of the graduate program GTR.
It is also important to re-enforce education on research ethics to prevent research misconduct. We
have shared the common notion that research failure is quite common even at the highly productive ITbM
and is an inevitable process to success, and that research misconduct is totally meaningless. Whereas weestablished the rule to store lab-notebooks and save original data, we are preparing the system tosave the original data on the cloud to prevent intentional data falsification by researchers. Openscience, in which original data is made public through databases and other means, should also be actively
promoted to make reproducible and transparent results a common property of humankind, thereby
contributing to the acceleration of research worldwide and the return of research outcomes to society.
Research Organization Management: ITbM has been recognized as an essential research institute for
NU to become a world-leading research university and was assigned as a permanent organization in March
2022. We recognize that diversity and organizational rejuvenation are important for the sustainable
development of ITbM. Following discussions at the WPI Program Committee, ITbM assigned one female PI
and two junior PIs (one female and one non-Japanese). ITbM continues to recruit junior PIs strategically,in view of nurturing young researchers and enhancing diversity.
Despite the unique independence of ITbM, ITbM’s Director and core members are having close contact
with the Chancellor, President, Trustee, and the related departments. While PhD students andTokai National Higher Education and Research System, Nagoya University - 3
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undergraduate students have been allocated to NU PI groups and several overseas PI groups, the Graduate
School of Science has made a system reform to officially allocate more PhD students, especially to ITbM’s
overseas PI groups from FY2022. We will further strengthen ties with the departments of NU and actively
contribute to the education of PhD students.

4. Plan for Promoting the International Circulation of World’s Best Brains* Describe your policy and concrete plan for promoting the international circulation of the world’s best brains, which is an importantfunction of the WPI Academy.

We believe the strong relationships between ITbM and external organizations are also quite important.
We will strengthen our international collaborative relationships with existing partners such as NSF-CCHF(US), RIKEN CSRS (Japan), Academia Sinica (Taiwan), and KALRO (Kenya). ITbM’s 5 world-leading
overseas PIs are also active to promote the internationalization of ITbM. They are sending a few researchers
from his/her institutes to ITbM every year and will continue this activity. In addition, the overseas PI groups
will be involved in the PhD course education from FY2022, which will attract PhD students from abroad
and accelerate internationalization.
ITbM recognizes the importance of fostering young researchers with an international perspective andhas been providing PhD students with research opportunities overseas. ITbM will continue this initiative
more actively by utilizing such as the Graduate Program WISE and the Joint Degree Programs.
ITbM will continue to host annual international symposia (ISTbM) and three international awards (Hirata
Award, Tsuneko & Reiji Okazaki Award, and Nagoya Medal of Organic Chemistry).

5. Plan for Disseminating the WPI Program Achievements*Describe your policy and concrete plan for disseminating WPI center achievements both within the host institution and to otheruniversities, especially their experience and know-how accumulated on establishing top world research institutes and advancing system
reforms.

As a Designated National University, NU continues to pursue system reforms to become a worldclass research university in line with President Matsuo's goal of "NU MIRAI 2020". In this context,
ITbM is positioned as NU's flagship research institute, and contributes to achieving the goal.
Establishment of measures to prevent research misconduct: In response to our case of
research misconduct at ITbM, ITbM and NU have worked together to take thorough measures toprevent research misconduct, establish a concrete action plan, and horizontally deploy it throughout
NU. The measures will be regularly discussed and revised as necessary. Through this endeavor, ITbM
and NU will protect researchers from research misconduct, and as a result, the research activities of
ITbM and NU will be promoted.
Establishment of the International Advanced Research Organization: NU established the
Nagoya University Institute for Advanced Research (NAIAS) to further strengthen its world-leading basic
research, and placed ITbM under its umbrella. The Institute for Advanced Research (IAR), which
implements next-generation research support programs such as WPI-next, was also placed under NAIAS,
and the know-how accumulated at ITbM is horizontally deployed.
Spread of the Mix Lab concept to promote interdisciplinary research: The ITbM Mix Lab
concept is being widely recognized at many institutions inside and outside of NU through the following
graduate program GTR, because of its high success in encouraging unexplored interdisciplinary research.
We will also communicate with other departments and spread our Mix Lab as good practices.
Establishment of a new graduate program with ITbM at its core: NU recognizes thesignificance of the Mix Lab concept and plans to extensively involve ITbM in the evolution of graduate
schools. NU and ITbM have put together a proposal for a program entitled "Graduate Program ofTransformative Chem-Bio Research (GTR)", as an application to the Doctoral Program for World-leading
Innovative & Smart Education (WISE Program) of MEXT, and was successfully selected in late 2018. In
GTR, ITbM is positioned as a hub for promoting interdisciplinary research in the field of natural sciences,and the designated faculty members of ITbM will be engaged in the education of PhD students throughsupervising collaborative research. An important aspect of this program is its ripple effect. Throughdiscussions to prepare the concrete plan, the ITbM spirit of Mix was widely shared among the cooperating
institutes and firms, spreading to the researchers on site. The GTR installed three Mix Labs so far to ensure
the success of the program. On the other hand, we also recognize that barriers still exist in organizational
structures in NU. We will continue to work with NU headquarters and the related departments to improve
graduate education at NU.
Establishment of an effective public relations system in NU: In cooperation with other WPI
institutes, ITbM has been engaged in various public relations and outreach activities. By sharing theexpertise and experience of ITbM, NU now has a system to send out international press releases

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highlighting the research accomplishments of the entire university. ITbM will further cooperate with NU
to establish a more efficient public relations system and organize outreach activities as a whole. It isalso notable that ITbM has established strong ties with high schools, particularly in the Tokai area. Manyof the researchers at ITbM have given lectures at high schools through this program. As a result, ourcutting-edge science attracts many high school students, and more importantly, many high school
teachers. The WPI Science Symposium in 2018 organized by ITbM was a focal point for these interactions.
We will share this experience with NU to continue improving our strategy to attract and encourage top
students.

6. Plan for Sustaining the WPI Brand* Describe your plan for sustaining and enhancing the WPI brand.

ITbM will sustain the WPI brand by further advancing our research activities as a top-level research
center. Based on the tight bond of chemistry, biology, and theoretical science built over the past 10 years,
we will add data science as a new pillar to explore new frontiers under the new director. We will involve
new researchers with diversity and generational change in mind, and establish a research hub that is evenmore recognized worldwide. We also recognize that outreach activities are keys to raising the value of thecenter and the WPI brand. We will further promote public relations activities and attract researchers fromaround the world. Expanding ITbM’s network will also contribute to building the WPI brand. So far 99 ITbM
researchers/PhD students have been promoted to faculty positions in academia, and act as ITbM supporters.
ITbM’s international symposia and awards will significantly contribute to increasing ITbM’s international
visibility to attract overseas researchers and PhD students as denoted above, which will also contribute to
the recognition of the WPI brand.

7. Support by Host institution* Describe measures that the host institution will take to support and sustain your Center.

ITbM is positioned as a flagship research institute in President Matsuo's initiative NU MIRAI 2020 and
the NU’s "Designated National University" concept. To secure the employment of ITbM’s faculty and staff
members, NU has launched the Nagoya University Institute for Advanced Study (NAIAS), and positioned
ITbM under this umbrella. Even under this new structure, the Director of ITbM retains the authority tomake decisions for matters regarding ITbM. NU and ITbM have undertaken the reorganization, consciousof maintaining the good relationships already established between ITbM with other departments/faculties
at NU. Eight NU PIs will continue their cooperation with their original faculties, and the students areallocated. While students were not allocated to the overseas PI groups at the beginning, it became possible
from FY2022.

8. Resource Allocation Plan

* Describe your plans over a 5-year period for allocating resources acquired from both the host institution (e.g., financial resources andpositions) and from external research funding to execute the Center’s functions and activities described above.
* In Appendix 4, enter concrete numbers in the Resource Allocation Plan.

At its inception, ITbM had 8 PI positions transferred to it from NU. In 2019, 7 more faculty positions for
ITbM were officially secured by the President-Management Point System and allocated to ITbM as tenure
positions. Since 2018, NU has been requesting to MEXT the budget (Gaisan Yokyu) with the highest priority
to strengthening ITbM, and so far 6 faculty positions have been allocated.
From FY2022, NU increases the support to secure additional 8 faculty positions and the selected
postdocs/staff who are essential to run ITbM. In addition, NU supports a junior PI position to promote theinternationalization and diversity of ITbM.
ITbM promotes industry-academia collaboration with the full cooperation of NU. In 2020, the ITbM
Consortium was renewed as the "ITbM / GTR Consortium" with the participation of researchers engaging
in chemistry & life science in the above-mentioned GTR program, and the ITbM’s research is expanding.
This consortium provides for the member-companies the latest unpublished achievements and also a placefor exchanging information among the companies and recruiting excellent students, thus functioning as aplace for discovering joint research between industry and academia.
ITbM will also promote the acquisition of diverse funds such as large competitive funds and fundraising
activities through the Nagoya University Foundation.

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Appendix 1-1

Appendix 1 List of Principal Investigators (Application for Academy Center Certification)* If the number of principal investigators exceeds 10, add rows as appropriate.
* Give age as of 1 April 2022
* For investigators who cannot participate in the center project from FY 2022, indicate the time that their participation will start in the “Notes” column.
* Enter the host institution name and the center name in the footer.

Name
1 Takashi YOSHIMURA*

2 Jeffrey W. BODE*

3 Cathleen M. CRUDDEN*

4 Kenichiro ITAMI*

5 Toshinori KINOSHITA*
6 Takashi OOI*

7 Keiko TORII*

8 Shigehiro YAMAGUCHI*

Current affiliation

Academic degree and current
specialties

Director, Professor
Institute of Transformative BioMolecules, Nagoya University
Professor of Organic Chemistry
Department of Chemistry andApplied Biosciences, ETH Zürich,
Switzerland
Professor
Department of Chemistry, Queen's
University, Canada

Dr. Agriculture
Specialties: Animal Physiology,
Systems Biology, Neuroendocrinology
Doctoral of Natural Science
Specialties: Organic Synthesis,
Peptide and Protein Chemistry,
Catalysis, Ligation and Bioconjugation
Ph.D
Specialities: Catalysis, Organic
Synthesis, Materials Chemistry,Dr. Engineering
Specialties: Organic Synthesis,
Catalysis, Pharmaceuti-cal Science,
Nanocarbon Chemistry
Dr. Science
Specialities: Plant Molecular
Physiology
Dr. Engineering
Specialties: Organic Synthesis,
Catalysis, Molecular Recognition(position title, organization, department)

Professor
Institute of Transformative BioMolecules, Nagoya University
Professor
Institute of Transformative BioMolecules, Nagoya University
Professor
Institute of Transformative BioMolecules, Nagoya University
Professor
College of Natural Sciences
The University of Texas at Austin
Investigator
Howard Hughes Medical InstituteVice-Director, Professor
Institute of Transformative BioMolecules, Nagoya University

Notes(Enter “new” or “ongoing”)

Effort(%)*
80

ongoing21

ongoing21

ongoing70

ongoing70

ongoing70

ongoing

Ph.D.
Specialties: Plant Development, Signal
Transduction, Stem Cell
Maintenance/Differentiati-on in Plants

21

ongoing

Dr. Engineering
Specialties: Main Group Chemistry,
Physical Organic Chemistry70

ongoing

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Appendix 1-1

9 Steve A. KAY*

10 Florence TAMA*

11 Wolf B. FROMMER*
12 Takeshi YANAI*
13 Yuichiro TSUCHIYA*

14 Azusa KAMIKOUCHI
15 Anuphon LAOHAVISIT

16 Quan PHUNG

17 Yoko MIZUTA

University and Provost Professor of
Neurology, Biomedical Engineeringand Biological Sciences, Director of
Ph.D.
Convergent Bioscience
Specialties: Chronobiology, Genetics,
Co-Director of the USC Norris
Biochemistry, Systems Biology
Center for Cancer Drug
Development,
Keck School of Medicine, University
Professor
Institute of Transformative BioPh.D
Molecules / Department of Physics,
Specialties: Computational Biophysics
Graduate School of Science,
Nagoya University
Professor, Heinrich Heine University
Dr. rer. nat.
Düsseldorf and Max Planck InstituteSpecialties: Biology
for Breeding Research
Professor
Dr. Engineering
Institute of Transformative BioSpecialties: Theoretical Chemistry,
Molecules, Nagoya University
Computatoinal Quantum Chemistry
Designated Professor
Dr. Agriculture
Institute of Transformative BioSpecialties: Plant Genetics, Chemical
Molecules, Nagoya University
Biology
Professor
Institute of Transformative BioMolecules, Nagoya University
Designated Associate Professor
Institute of Transformative BioMolecules, Nagoya University
Associate Professor
Institute of Transformative BioMolecules / Graduate School of
Science, Nagoya University
Designated Assitant Professor
Institute of Transformative BioMolecules, Nagoya University

10

ongoing50

ongoing21

ongoing70

ongoing70

new

Dr. Pharmaceutical Sciences
Specialities: Neuroscience

50

new

Ph.D.
Specialties: Plant Signaling, Plant
Physiology, Chemical Biology

80

new

Ph.D.
Specialties: Data Science, Theoretical
Science50

new

Dr. Science
Specialities: Plant Molecular
Physiology

80

new

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Appendix 2

World Premier International Research Center Initiative (WPI)
Number of Center Personnel
FY2022
Number of persons

Researchers％

63

Overseas researchers

20

31.7

Female researchers

20

31.7

Principal investigators (PIs)

17

Overseas PIs

7

41.2

Female PIs

5

29.4

Other researchers

27

Overseas researchers

2

7.41

Female researchers

7

25.9

Postdocs

19

Overseas Postdocs

11

57.9

Female Postdocs

8

42.1

Research support staffs

47

Administrative staffs

7

TOTAL

117

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Appendix 3

World Premier International Research Center Initiative (WPI)
Diagram of Organizational Management System- Diagram the Center’s organizational management system and its position within the host institution in an easily understood manner.

Tokai National Higher Education and Research System, Nagoya University-1
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