RIKEN CENTER FOR SUSTAINABLE RESOURCE SCIENCE

Advisory Council Report 2019

Center for Sustainable Resource Science Advisory Council
RIKEN, Yokohama, July 8-10, 20191

The third RIKEN Center for Sustainable Resource Science (CSRS) Advisory Council meeting was heldfrom July 8 to 10, 2019 at the RIKEN Yokohama Campus. The 2019 Advisory Council report andrecommendations are based on the comprehensive report of CSRS current activities and future goals(White Paper) provided by Director Dr. Kazuo Shinozaki, on presentations of five Flagship Projects
provided by the Deputy Directors, on research presentations provided by the Group Leaders, and thebiographies of CSRS Principal Investigators and Group Leaders. The report summarizes the evaluation
and recommendations of the CSRS Advisory Council and addresses the CSRS Directors report andfuture plans as well as the Terms of Reference by President Dr. Hiroshi Matsumoto and Director Dr.
Kazuo Shinozaki.
Members of the 2019 RIKEN CSRS Advisory Council
Dr. Wilhelm Gruissem, Chair
Department of Biology, ETH Zurich, Switzerland(Plant Biology and Biotechnology)(Synthetic Organic Chemistry)Dr. Hirokazu Arimoto
Professor, Graduate School of Life Sciences, Tohoku University, Japan
Dr. Cathleen Crudden(Catalysis and Material Chemistry)
Professor, Department of Chemistry, Queens University, Canada(Plant Developmental and Systems Biology)
Dr. Dirk Inzé
Professor and Director, Center for Plant Systems Biology, VIB/Gent University, Belgium
Dr. Kenichiro Itami(Organic Chemistry and Catalysis)
Professor and Director, Institute of Transformative Bio-Molecules, Nagoya University, Japan
Dr. Chaitan Khosla(Organic and Physical Chemistry, Catalysis)
Professor, Departments of Chemistry and Chemical Engineering, Stanford University, USA(Plant Physiology, Developmental Biology)
Dr. Junko Kyozuka
Professor, Graduate School of Life Sciences, Tohoku University, Japan
Dr. Yasuo Ohnishi(Microbiology)
Professor, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan
Dr. Kirsi-Marja Oksman-Caldentey(Synthetic Biology, Industrial Biotechnology)
Research Manager, VTT Technical Research Centre Ltd, Finland
Dr. Mitsuo Sawamoto(Polymer chemistry and synthesis)
Professor, Institute of Science and Technology Research, Chubu University, Japan
Dr. Michinori Suginome(Organometallic, Synthetic, Polymer Chemistry)
Professor, Department of Synthetic Chemistry and Biological Chemistry, Graduate School ofEngineering, Kyoto University, Japan

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Executive Summary
Since the evaluation in 2016, the RIKEN Center for Sustainable Resource Science (CSRS) has madeexcellent progress in integrating plant biology, chemistry and chemical biology by strengthening thebalance between these disciplines and catalyzing innovative synergistic collaborations among the
research groups. Many CSRS scientists are highly visible international leaders of innovation in theirfields. CSRS research is now organized around five strategic flagship projects that represent the
research strength of the Center and the new strategic focus on biotechnology and metabolicengineering. Both basic and applied research projects address important United Nations Sustainable
Development Goals to provide important solutions for national and global societal challenges. CSRS
and RIKEN in general are critical technology hubs that drive disruptive research and development inJapan and beyond. CSRS efforts of translating basic research into innovative applications are rapidly
expanding but must be met by stronger industry investments and entrepreneurial efforts to realize
their full potential. With the implementation of new employment rules during the next four years,
CSRS also has important opportunities of evaluating its research portfolio to expand and balance
strategic directions as well as improving gender balance and international diversity among its
research leaders and staff. With this, CSRS will continue its successful path of an internationallyleading RIKEN research and technology center.

General Comments and Recommendations
CSRS originated from the Plant Science Center that was established in 2000. A major effort was madein 2013 to merge plant science with chemical biology, catalysis and polymers. The Biomass Research
Program was integrated in 2015. This opened many opportunities but also created challenges
because not only different disciplines were merged but also different cultures and research programs
across three physically separated campuses (Yokohama, Wako and Tsukuba). During the last six years
CSRS has become an internationally leading research center that is unique in combining plant andmicrobial research with chemical biology, chemical catalysis and polymer science to drive
unprecedented frontier research and innovative interactions between these disciplines.
Director Kazuo Shinozaki has made tremendous and successful efforts in leading the integration of
the different disciplines and facilitating interactions among the research areas, encouraging
researchers from different disciplines to collaborate in a supportive atmosphere, stimulate andsupport the development of new leading-edge research projects, and establish the international
visibility of CSRS. The performance of CSRS as a whole is outstanding and world class. There are many
exciting research results that have been reported since the 2016 evaluation with many new
publications in high-ranking journals. Most research projects are closely aligned with the mission of
CSRS. The leadership of Dr. Shinozaki has assured the continuation of a high level of research
performance and innovation. Clearly, CSRS is now the important pillar of the RIKEN mission to drive
innovative research and technology development for Japan’s society and also internationally. The
Advisory Council affirms the values that CSRS bring to RIKEN in providing a world-class group of
scientists at the interface between chemistry and biology outside the biomedical enterprise. Dr.
Shinozaki must be highly commended for his inspiring leadership and achievements in building CSRS.
At the same time he maintains a world-leading research program in abiotic stress tolerance that has

3received many awards, acknowledgements as highly cited researcher, and the honor of being a
Person of Cultural Merit in Japan.
The 2016 Advisory Council report recognized the accomplishments of CSRS and at the time
recommended the development of a visionary strategic plan that focuses on flagship projects. These
flagship projects should emphasize the RIKEN mission of driving research and technology innovation
as well as the CSRS mission of developing new interdisciplinary research in sustainable resource
development to increase the visibility of the institute.
In 2019 the Advisory Council is pleased to see that CSRS has actively and positively taken up therecommendation. In discussions with the Group Leaders in a bottom-up process CSRS establishedinnovative and creative flagship projects. They focus on innovative plant biotechnology, metabolic
genome engineering, innovative catalysts, leading edge polymers and advanced research andtechnology platforms that reflect the CSRS research areas as well as their integration and increasing
cross-cutting activities. The Advisory Council was impressed with the ongoing integration process,the progress of CSRS research and development during the last three years, and the identificationand development of the flagship projects. Their strategic focus on the United Nation 17 Sustainable
Development Goals (SDGs), in particular SDGs 2, 3, 7 and 12-15, is important for Japan andinternationally because they address human health, climate change mitigation as well as sustainable
and safe food production. The Advisory Council agrees that flagships are important for focusing the
research and communicating the science to the public. The contributions from CSRS, and RIKEN ingeneral, to SDGs is a strongly added value to the mission of the institution.
The Advisory Council recommends that the flagship projects must better explain to the public andpoliticians how their excellent research results and innovations can be translated into practicalapplications and impact in breeding and crop production for the benefit of society.
The interdisciplinary expertise available in CSRS has great potential for collaborations to drive
innovative research and development. A few laboratories are already integrating their research
activities well, however, overall this potential has not been fully realized yet. The Advisory Council
acknowledges the important progress that CSRS has made in strengthening chemical biology andintegrating it with plant science during the last few years. But it also finds that there are still many
excellent individual research projects running simultaneously, especially in plant sciences, which do
not take advantage of expertise available in other laboratories. Often this prevents research fromgoing deep enough. The Advisory Council agrees that researchers should keep their individual
projects, but should increase discussions among the groups to identify overlapping interests andsynergies for intensive collaborations.
In going forward, the Advisory Council also recommends increased efforts of bridging the flagshipprojects, for example by incentivizing new cross-cutting research projects, by expanding theinteractions between plant science, polymers and catalysis, and by further integrating plant scienceand biotechnology. CSRS researchers agree that integrating plant biology and chemistry is a key issue.
The Advisory Council understands and appreciates that the two main locations of CSRS research on
the Wako and Yokohama campuses is often not conducive to close collaborations. The Advisory
Council therefore recommends to increase efforts of involving the young PIs and Group Leaders in
defining and planning the research in and between the flagship projects, for example in regular4scientific retreats to stimulate collaborations. The Advisory Council also recommends to further
strengthen chemical biology and synthetic chemistry, especially through interactions with other
RIKEN research groups in these fields, and mixing them more strongly with the plant field, bothscientifically and physically. In addition to the collaborations with the Institute of transformative
Biomolecules at Nagoya University and the Max-Planck Organization in Germany, CSRS should
identify and reach out to other international chemical biology and synthetic chemistry groups tofoster innovative collaborations with CSRS research groups. The Advisory Council is convinced thatcollectively these measures will facilitate CSRS in leading the world in innovation.
CSRS is very successful in training young scientists and helping them to establish their own careers inacademia and industry, primarily in Japan. The Advisory Council recommends that CSRS should now
also take a broader role in facilitating science education and research especially in Asian countries,
but also in Europe and the U.S., by attracting young scientists to RIKEN for training and futurecollaborations. This will strengthen the internationalization in CSRS and further increase the visibilityof the institute. Group leaders agree that Asia is becoming increasingly important in world and thatbuilding strong networks with other Asian countries will give CSRS a competitive advantage.
Nationally, Japan is experiencing a rapidly aging society and among the younger generation a generallack of interest in scientific careers. This phenomenon is also observed in other countries but isexacerbated in Japan by dwindling opportunities for young people in Japan of building successful
scientific careers in academia and industry. The Advisory Council recommends that CSRS, and RIKEN
in general, increase efforts of reaching out to students in high schools and universities to makescientific research attractive again to the young generation. This could be done, for example, by
providing short term internships that give young students the opportunity to become involved inresearch projects at an early age.
CSRS has already established productive collaborations with industry to facilitate translation of theirresearch results. The White Paper lists a few concrete examples of such industry collaborations(Yokohama Rubber Company and Zeon Corporation for isoprene biosynthesis, Kaneka Corporation
for developing a novel biopolyester into a new material with high biocompatibility, or Euglena
Company for biofuels production). In his presentation Director Shinozaki showed interactions andcollaborations with more than 40 other companies. However, the actual financial support provided
by these companies to the CSRS research program currently amounts to only 10% of the CSRS annual
budget. This is surprising and the Advisory Council questions if the collaboration with 40 companies
involves commercial development in all cases. If they do, invoicing per company must be very low
and CSRS scientists do not market their expertise appropriately. The Advisory Council recommends
that efforts should be expanded to increase industry funding and visibility for societal impact. Morespecifically, CSRS should consider engaging in industry collaborations at an earlier stage of researchand development without forgoing the publication of their research results high-visibility journals.
CSRS and RIKEN should develop mechanisms and incentives for companies to increase their financial
investments in pre-commercial research and development from which they ultimately profit. This
would also help CSRS researchers to facilitate the translation of basic research results into promising
new applications. The RIKEN Innovation Company is an important venue to explore such earlyinteractions with industry. The Advisory Council also encourages CSRS scientists to explore how theirresearch could be translated into own entrepreneurial opportunities. The CSRS spin-off companies
Ac-Planta for commercialising acetic acid application for improved crop performance (founded in52018) and the Japan Moss Factory for production of moss culture and phytoremediation (founded in2019) are good examples of translating basic research results into promising commercial applications.
The CSRS budget has been essentially flat for the last 5 years while internal budget allocations haveshifted and competitive external funding generated by the scientists has probably reached a ceiling.
CSRS researchers must be strongly commended for their efforts in attracting competitive funding fortheir research projects. But this targeted external research funding and the shrinking direct CSRS
funding from RIKEN make it difficult for the Director and the leadership to develop new researchareas and incentivize cross-cutting activities. The Advisory Council understands that in times ofshrinking government research funding this is difficult to change. Therefore the Advisory Council
recommends that CSRS considers and explores novel funding sources. While the culture of private
philanthropy is not yet strongly developed in Japan compared to the U.S., the CSRS flagship projects
to address SDGs are a strong basis to approach national and international foundations as well asaffluent private individuals who share the vision of CSRS to make a difference through innovative
research.

Comments and Recommendations on Flagship Projects
Innovative Plant Biotechnology
The Innovative Plant Biotechnology Flagship focuses on the development of plants with high yieldand resistance to environmental stresses to secure sustainable food and biomass production forsociety. This flagship is led by Dr. Minami Matsui and has 3 research groups, 4 research teams and 3
research units. Most of them use the model plant Arabidopsis for their research but increasingly alsotranslate their results to important crop plants such as cassava and rice. The individual research
projects of the Innovative Plant Biotechnology Flagship are all excellent and exciting, as isconvincingly demonstrated by the evaluations of the individual group leaders. Scientists arecontinuing to make ground-breaking discoveries, mostly in the model plant Arabidopsis, andcontinue to publish their work in top journals. Excellent examples include the discoveries of small
molecules such as the CLE25 peptide, acetic acid and ethanol that mediate drought tolerance andhave interesting potential for applications for crops in the field. Similarly, the enzyme galactinol
synthase, which was first reported in Arabidopsis in 2002 to catalyse the production of the raffinose
family of oligosaccharides, was recently shown to increase yield in drought conditions when
overexpressed in upland rice. The newly established RIKEN integrated plant phenotyping system will
facilitate precise growth measurements and discoveries of control mechanisms.
While the individual projects of the Innovative Plant Biotechnology Flagship continue to produce
important discoveries, the Advisory Council recommends that their scientists also focus morestrongly on cross-cutting aspects of their research projects to accelerate translation andbiotechnology development. Several of the groups work on drought tolerance, but they do notappear to collaborate in order to facilitate the contextual understanding of their results. For example,
if CLE25-type peptides that were discovered in Arabidopsis roots are also found in crop plants tocontrol stomatal closure and water-deficit control, then it will be important to understand how thismechanism relates to the functions of acetic acid and the potential new hormone karrikin in themodulation of drought responses. Some of the groups have initiated collaborations with chemical

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biologists to probe biochemical pathways and mechanisms with small molecules. The Advisory
Council recommends intensifying these interactions and taking advantage of the available unique
RIKEN chemical library resources to facilitate our understanding of biological processes. The Advisory
Council also recommends to better integrate the analysis of large-scale data by including machinelearning and automated phenotyping to identify, probe and modify gene regulatory networks rather
than focusing on individual genes. While understanding the function of individual genes in plantstress remains important, it is now increasingly clear that different abiotic stress responses, which in
the field often occur together (such as drought and heat) are mediated by complex integrated
regulatory networks. This is also the case for biotic stress responses. The Advisory Council
recommends that researchers of the Innovative Plant Biotechnology Flagship organize regularmeetings to discuss their project results and find common ground for collaborations. They should
also take advantage of synthetic biology approaches such as the construction of regulatory geneswitches to drive disruptive innovation in plant and microbial research with links to catalysis andpolymer science. The Advisory Council is convinced that this will facilitate the implementation oftranslational work to improve crop performance and biomass production.
Metabolic Genome Engineering
The Metabolic Genome Engineering Flagship focuses on maximizing the capabilities of plants andmicroorganisms (‘smart organisms’) in expanding the production and use of bioproducts to replacefossil fuel-based chemical production processes with sustainable production systems. This is basedon a strong vision how to reach impact in metabolite engineering and production by also integrating
metabolic modelling, which already has high international visibility. The flagship project is led by Dr.
Kazuki Saito and includes five research groups with expertise in plant, microorganism andenvironmental research. The large potential of this project has already been demonstrated byengineering pathways for triterpenoid/steroid biosynthesis (e.g., the natural sweetener glycyrrhizin),
neolignane biosynthesis, butadiene or maleate bioproduction. The engineering of the isoprenebiosynthesis for natural rubber production using an artificial metabolic pathway is another exampleof the capabilities that are being developed in this flagship. More recently, researchers are also using
genome editing technologies (CRISPR-Cas, TALEN) to engineer metabolic pathways and produce newmetabolites. This is clearly an exciting development with significant potential. The flagship project
has identified bioinformatics and mathematical modelling as an important basis for the research
program and therefore developed a web-based platform (PASMet, Prediction, Analysis andSimulation of Metabolic networks) to support these activities. But the Advisory Councils finds thatthe available expertise in bioinformatics and modelling is still sub-critical in this flagship, and CSRS asa whole, and therefore recommends to strengthen these important areas.
Innovative Catalysts
The Innovative Catalysts Flagship project is led by Dr. Zhaomin Hou and has two research groups andthree research teams. This flagship project focuses on the development of more efficient andselective catalysts for synthesis of fine chemicals and functional materials to reduce the consumptionof fossil fuels and increase the use of natural renewable resources. This flagship already has strong
impact, high international visibility and outstanding accomplishments. The achievement of efficient
catalytic ammonia formation in the reaction of N2 and H2 under mild conditions is an excellent

7example of an alternative to the energy-intensive Haber-Bosch process. The iron-catalyzed selective
direct C–H/C–H cross-coupling reaction of two substrates in a stoichiometric amount is an importantworld-class demonstration of using earth-abundant metal catalysts for organic synthesis. Similarly,
the development of reusable catalysts is another example of innovation driven by the researchers inthis flagship who are internationally recognized for their achievements. For example, Dr. Mikiko
Sodeoka is the first female scientist in Japan to receive Cope Scholar Award of the American
Chemical Society, which reflects her international leadership.
Considering the small size of the Innovative Catalysts Flagship, the Advisory Council discussed at
length how the current exciting achievements of this flagship can benefit renewable biomass
resources. The Advisory Council recognizes that person-power in this flagship remains limited andrecommends that researchers forge closer interactions with the Innovative Plant Biotechnology
Flagship for additional opportunities of using novel catalysts and biomass for product development.
The Advisory Council also recommends looking for additional resources to expand the number of
researchers in inorganic chemistry and solid catalysis for developing new frontiers, for example incollaboration with industry.
Leading-Edge Polymers
The Leading-Edge Polymers Flagship Project is led by Dr. Hideki Abe and focuses on the developmentof new functional polymer materials with strengthened specific or interesting novel functions. It is
the smallest of the CSRS flagship projects and consists of the Advanced Catalysis Research Group (Dr.
Hou) and the Bioplastic Research Team (Dr. Abe) and the Biomacromolecules Research Team (Dr.
Numata). The flagship project is already producing interesting novel polymers, such as self-healing
ethylene-anisylpropylene copolymers or polymers with excellent shape-memory properties. The
chemo-enzymatic synthesis of peptides is another example of the rapid progress in this flagship thathas the potential for further development into a novel chemical protein synthesis platform. The
current use of the plant substrates vanillin or gallic acid for building novel polymers such as GDA
polyesters, however, is not novel. These and similar plant-derived substrates are also used byresearch groups in other countries and therefore they are not very original for RIKEN as a leading
institution. The Advisory Council recommends to broaden the scope in utilizing biomass substrates todevelop innovate and environmentally-friendly polymers (for example, those that under seawaterconditions degrade within three months). The Advisory Council also recommends to explore andevaluate opportunities from close collaborations with the Metabolic Genome Engineering Flagship totake advantage of engineering metabolic pathways for novel metabolites that can become the basisof innovative polymers.
Technology platforms
The Advanced Research and Technology Platforms Flagship is excellent and of national andinternational strategic importance. The flagship is led by Dr. Hiroyuki Osada and Dr. Kazuki Saito andinvolves four groups on the Yokohama campus and seven groups on the Wako campus. The Advisory
Council discussed if technology platforms should be considered a flagship project. It acknowledges
the unique mission of RIKEN of building world-class and cutting-edge technology platforms thatwould be difficult to realize in universities. Therefore it is warranted to give technology platforms a8

flagship status, especially since they are accessible for all researches in Japan and internationally.
Research in the flagship projects is strongly driven by small molecules and metabolites as well as
genome-centred and bioinformatics approaches utilizing large molecular and genome databases incombination with machine learning applications. The Advisory Council agrees that the Advanced
Research and Technology Platforms have an important service function and therefore recommends
that the scientists should make strong efforts of bridging the other flagship projects. The Advisory
Council also recommends that in addition to the technology support role, the Advanced Research
and Technology Platforms should be facilitating cutting-edge, disruptive technology development tostrengthen RIKEN’s national and international position as a technology leader.
The strengths of the Advanced Research and Technology Platforms are the available expertise andinstrumentation for metabolomics, proteomics and high-resolution microscopy (including cryo-EM),
leading edge technologies, and chemical library resources. It is planned to integrate and expand
bioinformatics for building a comprehensive information infrastructure to support the other flagshipprojects. However, there is also genuine concern that the shrinking CSRS budget will no longer besufficient to maintain the internationally leading edge of this flagship. The Advisory Council shares
this concern and recommends that RIKEN therefore continues and ideally increases the necessary
instruments and infrastructure investments to keep the excellence high. The CSRS platform resources
are highly attractive at the international level. The Advisory Council recommends that RIKEN shouldmake strong efforts of maintaining and expanding this international treasure to attract the mostpromising young scientists in Japan who can drive leading-edge method and technology
development. As a rapidly moving field, technology development is difficult to predict. The Advisory
Council therefore recommends to carefully monitor the technologies that need to be developed andimplemented for CSRS to keep its international competitive edge.
The international strength and leadership of RIKEN in chemical biology is based on a very small
number of research groups, most prominently represented by Dr. Hiroyuki Osada. These groups havedeveloped cross cutting activities with plant sciences to probe biochemical pathways with small
molecules. The Advisory Council recommends that CSRS and RIKEN should continue to search forexcellent early career scientists to continue strengthening chemical biology. The Advisory Council
further recommends that CSRS should develop a plan for stewardship for the natural product librarythat Dr. Osada has developed over many decades. For example, the natural product library could be
an important opportunity and starting point for a new entrepreneurial venture supported by the
RIKEN company to rejuvenate natural product discovery in the 21st century.

CSRS-associated collaborative research activities and co-operations
The Drug Discovery Platforms Corporation Division, the RIKEN-Max Planck Joint Research Division for
Chemical Systems Biology and the RIKEN-KRIBB Joint Research Unit are administered by CSRS but
have separate budget lines. The Drug Discovery Platform, which was established as a 10-year
program during the Presidency of Dr. Ryoji Noyori and is led by Dr. Minoru Yoshida, is focused on the
discovery of interesting new compounds for medical applications, such as the moleculartryptolinamide that inhibits phosphofructokinase 1 for the treatment of patients with mitochondrial
dysfunctions. Increasingly the research is shifting from small molecules to the discovery of othermolecules with therapeutic potential. While the Drug Discovery Platform continues to make9

important contributions, its future is uncertain. Discussions are underway to extend the program
until 2024. The Advisory Council recommends that RIKEN should evaluate its role in high-throughput
screening and drug discovery for medical diseases. A commitment to continued leadership in thisfield will give the Drug Discovery Platform more planning security and longer-term stability. This also
requires financial investments to assure that RIKEN remains competitive at the national andinternational levels.
The RIKEN-Max Planck Joint Research Division for Chemical Systems Biology includes threescientists from RIKEN and two scientists from the Max Planck Institutes of Molecular Physiology and
Colloids & Interfaces. At RIKEN this research division is led by Dr. Hiroyuki Osada. In addition to joint
screening for bioactive compounds and identification of their targets, the participating laboratories
also actively exchange young researchers and chemical compounds. The recently established RIKENKRIBB Joint Research Unit exploits the complementary strengths of three chemical biology scientists
each from CSRS and the Korea Research Institute of Bioscience and Biotechnology. At RIKEN the joint
research unit is led by Dr. Hiroyuki Osada. The joint research unit focuses on the screening andisolation of novel bioactive compounds from bacteria and fungi as well as the identification of theirtargets. A primary goal is the exchange of scientists and development of know-how.
The Advisory Council finds these to be valuable activities and recommends to evaluate otheropportunities for synergistic activities with leading institutions overseas because this will further
expand and strengthen the internationalization of CSRS. While the number of CSRS researchers from
India other Asian countries is increasing, CSRS continues to find it difficult to attract young scientists
from the U.S. and Europe. Although CSRS lists 26 international collaborations, mostly with
universities, the Advisory Council found it difficult to evaluate their effectiveness in strengthening theinternationalization of CSRS by promoting the exchange of scientists and attracting young
researchers from other countries to RIKEN.
At the national level CSRS has established a partnership and cooperation with Nagoya University andthe WPI Institute of Transformative Biomolecules for joint research and utilization of infrastructure
and resources. Other co-operations were established with Yokohama City University and Saitama
University for access to the graduate programs, which allows CSRS scientists to supervise PhD
students. The Advisory Council recommends to strengthen and expand such co-operations, also withthe goal of building more joint graduate program for the benefit of university PhD students who arebeing trained at RIKEN.
The recently established Integrated Symbiology Project (iSYM) is a cross-cutting RIKEN program led
by Dr. Ken Shirasu with an independent budget that involves researchers from several RIKEN
research departments. The goal is the utilization of symbiotic systems in humans, animals,
agriculture and the environment to transform the bioindustry. The research efforts, which aresupported by cutting-edge technologies and instruments, have already generated interesting results
in a short time. The Advisory Council applauds the RIKEN initiative to bring its scientists fromdifferent fields and with different expertise together to open new research directions. This clearlyreflects the strength and competitive advantage of RIKEN and could help to increase its visibility at
the national level by exploring the Japanese gut microbiome. But it was not clear to the Advisory
Council why the iSYM project focuses only on symbiotic interactions but excludes disease caused by10

microbes, especially when those disrupt beneficial symbiotic interactions for the human, animal andplant hosts.

CSRS personnel and administrative management
The Advisory Council appreciates that the CSRS Directors are now engaging the group leaders inplanning processes and discussions of research directions. The development of the flagship projects
is a good example for this bottom-up process because it allows researchers to support and identify
with their mission. The Advisory Council recommends that this engagement can be further
strengthened by clearly communicating how decisions in CSRS are made, by including the groupleaders in discussions on the future of CSRS and longer-term planning beyond the current flagshipprojects or defining new flagship projects. In addition to the monthly CSRS group leader meetings,
the Advisory Council recommends to hold regular annual CSRS retreats to build community spirit andfacilitate collaborations among the researchers. Despite significant progress, group leaders see theintegration of plant biology and chemistry and interactions between the Wako and Yokohama
campuses still as challenges that need to be overcome. The Advisory Council also recommends toestablish an effective career path development program in CSRS to evaluate the potential of young
scientists and help them chart their future.
The new government employment laws impact current and future employment at RIKEN and willaffect many staff members with fixed-term contracts and research areas, also in CSRS. This isparticularly relevant for the historically-grown but currently imbalanced employment contracts
between the Wako campus where most group leaders have tenured positions and the Yokohama
campus where most group leaders have fixed-term contracts. However, the Advisory Council isconvinced that the employment transition in RIKEN is also a timely and important opportunity forincreasing internationalization, diversity and gender balance, as well as building new research areas
in CSRS. The Advisory Council strongly supports Dr. Saito, who will lead CSRS beginning in April 2020,and his plans for continued integration of CSRS’s existing pillars of scientific strength as well as hishuman resource plans necessitated by changes mandated by the Japanese government. The Advisory
Council recommends that all balanced employment and hiring decisions in CSRS must be the result oftransparent processes and based on clear policies and evaluation mechanisms for recruitment andpromotion to indefinite term appointments.
The recruitment and promotion of female scientists in CSRS remains ineffective. Although CSRS has awell-balanced gender distribution at the postdoc, PhD and technical research levels, this does nottranslate to the group leader level where the number of female scientists is still below 20% andremains unchanged since the last evaluation in 2016. Although CSRS has made efforts to recruit
female group leaders, the Advisory Council recommends that these efforts should be strengthened.
For example, future tenured positions should be used as an opportunity to recruit excellent female
scientists to research leadership positions. The Advisory Council recommends to aggressively
promote excellent female scientists to leadership positions also outside of CSRS. For example, inrecognition of her outstanding achievements Dr. Sodeoka should also assume a leading role in RIKEN

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in addition to her CSRS Group Leader position. Additional efforts to recruit non-Japanese female andmale researchers also need strengthening.

Recommendations from the CSRS Advisory Council to President Dr. Hiroshi Matsumoto
The Advisory Council reviewed the current CSRS research achievements and its 7-year plan withrespect to the terms of reference provided by RIKEN President Dr. Hiroshi Matsumoto and CSRS
Director Dr. Kazuo Shinozaki. Since the 2016 review, CSRS research progress and achievements
continue to be excellent and contribute to the RIKEN mission and societal progress. The SWOT
analysis is comprehensive and appropriately identifies the strengths and weaknesses of CSRS as wellas the opportunities for further development. These have been discussed in detail above andrecommendations on the SWOT analysis are summarized below.
TOR 1: CSRS research achievements, contributions to society and consistency with 7-year plan
CSRS research is recognized nationally and internationally with an impressive output of outstanding
quality research papers, also as a result of excellent technology platform support. CSRS continues tosynergize plant science, catalytic chemistry and chemical biology and has bundled research in thesedifferent disciplines into five strategic flagship projects, including biotechnology and metabolicengineering. Based on this CSRS will create novel scientific approaches, also through increasing andstrengthening synergistic interactions with other chemistry and chemical biology research groups in
RIKEN to maintain international competitive leadership. The five CSRS flagship projects address
important United Nations sustainable development goals and therefore make important
contributions to society. They are consistent with the CSRS 7-year plan and RIKEN mission of driving
innovative research and technology development for the benefit of society.
TOR 2: CSRS SWOT analysis
Strengths in management: CSRS brings together scientists from plant biology, chemical biology andchemistry into a unique and highly successful research institute with excellent output. The
comprehensive and balanced SWOT analysis critically analyzes the progress and achievements of
CSRS since the 2016 review. Director Dr. Shinozaki has excellently managed the integration ofdifferent disciplines in CSRS. He led the development of flagship projects, has made new
appointments of promising young group leaders to strengthen chemical biology and chemistry,
implemented important national and international collaborations, and continued efforts to increase
diversity. These accomplishments provide an important foundation for the future direction of CSRS
with the visionary leadership of the new Director Dr. Saito, whose plans are strongly supported by
the Advisory Council.
Weaknesses: The location of CSRS scientists on the Wako, Yokohama and Tsukuba campusesremains an obstacle for building strong synergies and close research collaborations as well as
frequent personal interactions among the group leaders and researchers from the different

12disciplines. The new CSRS building on the Wako campus has relieved the situation somewhat. The
decreasing CSRS operating budget and internally shifting budget allocations present a challenge forthe Director and researchers to maintain excellence and the international leadership of CSRS. RIKEN
has been generally successful in promoting their fixed-term contract researchers to good positions inacademia and industry. But the declining number of PhD students in Japan and scarce number ofacademic positions to build long-term careers is making the hiring of talented young researchers andpromotion to independent positions outside of RIKEN increasingly difficult.
Opportunities: The focus of the newly developed CSRS Flagship Projects on sustainable development
goals defined by the United Nations allows CSRS to strengthen interactions with the society in Japan.
They can raise awareness for the importance of research and acceptability of new breeding tools
such as genome editing to address challenges for sustainable agriculture, food security and reducing
the societal footprint of greenhouse gases. They are also opportunities to translate basic research
into applied research for the benefit of industry, not only in Japan but globally.
Threats: The transition to the new government employment policies and increased number oftenured positions by 2023 are perceived as a threat. But if managed well and communicatedtransparently, hiring and tenure decisions in CSRS over the next four years will become an
opportunity to focus research programs, build new research directions, and achieve an optimal
strategic balance between the five flagship projects. The stagnant budget, increasing labor costs andceilings to competitive public funding are of concern for future developments in CSRS. But this could
be mitigated by exploring philanthropic funding sources and by expanding collaborations withindustry, also in promising basic research and technology development.
TOR 3: Collaborations, including those in Science and Technology Hub program
CSRS has already established important and close collaborations with Nagoya University and theInstitute of Transformative Biomolecules. Collaborations with Yokohama City University and Saitama
University provides access to their graduate programs and PhD students. International researchcollaborations and co-operations involve, for example, the Max-Planck Society in Germany, Michigan
State University in the U.S., the Korea Research Institute of Bioscience and Biotechnology, and theAgricultural Genetics Institute in Vietnam. The effectiveness of collaborations with otherinternational universities and research institutions that are part of the RIKEN International Program
Associates are more difficult to evaluate. The CSRS Advanced Research and Technology Platforms
Flagship Project has high international visibility and is of central importance for RIKEN’s efforts ofbecoming a science and technology hub. The internationalization of the CSRS research staff isprogressing but needs to be accelerated and further strengthened.
TOR 4: Principal investigators
The principal investigators embrace the CSRS flagship projects and 7-year plan. Their research
programs are aligned with the mission of the Center and they increasingly engage in synergistic andproductive collaborations with colleagues from different disciplines inside CSRS, nationally andinternationally. The performance of the CSRS PIs is uniformly excellent and meets highest
international standards. They are highly successful in attracting competitive research funding, which13

now represents more than 30% of the annual CSRS budget. All PIs publish in leading journals, manyare international leaders in their field, and several are highly cited researchers during the last five
years, exemplifying the international impact of CSRS research. The PIs manage their laboratories andresearch programs well. They actively and effectively engage in the training and mentoring of earlycareer scientists, helping them to develop successful research projects and finding positions andcareers outside of RIKEN. They also have a role in translational research and attracting industry
interest and funding. This aspect will be further strengthened by the flagship projects and expanded
interdisciplinary collaborations.

Comments on the requests from the CSRS Director, Dr. Kazuo Shinozaki
The comments and advice of the CSRS Advisory Council on the newly started five flagship projects in
CSRS are provided in the above report. The individual PI evaluations are attached to the CSRS
Advisory Council report.

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The transition to the new government employment
policies is perceived as a threat but also provides
opportunities to achieve an optimal strategic balance
between the five flagship projects. The declining CSRS
operating budget and ceilings to competitive funding
are of concern for new developments in CSRS.

The focus of the Flagship Projects on sustainable
development goals allows CSRS to strengtheninteractions with society and raise awareness for theimportance of research to address challenges forsustainable agriculture, food security and reducing
the societal footprint of greenhouse gases.

CSRS has established important and close collaborations with Nagoya University and the Institute ofTransformative Biomolecules. Co-operations with Yokohama City University and Saitama University provide
access to graduate programs and PhD students. International research collaborations and co-operations arewell established, for example with the Max-Planck Society in Germany. The CSRS Advanced Research andTechnology Platforms Flagship Project has high international visibility and is of central importance for RIKEN’s
efforts of becoming a science and technology hub. The internationalization of the CSRS research staff needs tobe accelerated and further strengthened.

The problem of CSRS scientists located on three RIKEN
campuses and the decrease in operating funds havebeen clearly identified. The declining number of PhD
students in Japan and scarce number of academic
positions becomes increasingly problematic for PI’s.

Director Dr. Shinozaki has excellently managed theintegration of different disciplines, developed
flagship projects, and made new appointments inchemical biology and chemistry. The new Director Dr.
Saito has a strong vision for the future of CSRS.

TOR2

TOR3

CSRS research is recognized nationally and internationally with an impressive output of outstanding quality
research papers, also as a result of excellent technology platform support. CSRS continues to synergize plantscience, catalytic chemistry and chemical biology and has bundled research in these different disciplines into
five strategic flagship projects, including biotechnology and metabolic engineering. Based on this CSRS will
create novel scientific approaches, also through increasing and strengthening synergistic interactions withother chemistry and chemical biology research groups in RIKEN to maintain international competitive
leadership. The five CSRS flagship projects address important United Nations sustainable development goals
and therefore make important contributions to society. They are consistent with the CSRS 7-year plan and
RIKEN mission of driving innovative research and technology development for the benefit of society.

TOR 1

Recommendations from CSRS AC to
President Hiroshi Matsumoto

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TOR 4

The PI’s manage their laboratories and research programs well. They actively and effectively engage in the
training and mentoring of early-career scientists, helping them to develop successful research projects andfinding positions and careers outside of RIKEN. They also have a role in translational research and attracting
industry interest and funding. This aspect will be further strengthened by the flagship projects and expanded
interdisciplinary collaborations.

The performance of the CSRS PI’s is uniformly excellent and meets highest international standards. They arehighly successful in attracting competitive research funding, which now represents more than 30% of theannual CSRS budget. All PI’s publish in top journals, many are international leaders in their field, and several
are highly cited researchers during the last five years, exemplifying the international impact of CSRS research.

The principal investigators embrace the CSRS flagship projects and 7-year plan. Their research programs arealigned with the mission of the Center and they increasingly engage in synergistic and productive
collaborations with colleagues from different disciplines inside CSRS and RIKEN, as well as nationally andinternationally.

Results of PI Evaluations—Overview