Advisory Council Report in 2019
for RIKEN Center for Biosystems Dynamics ResearchAugust 19-22, 2019
Introduction
The Advisory Council (AC) of the RIKEN Center for Biosystems Dynamics Research(BDR) met in Kobe from 19-22 August 2019 to review the Center’s new research
directions and achievements. BDR was established in 2018 by reorganizing threecenters, Center for Developmental Biology (CDB), Center for Life Science Technology(CLST), and Quantitative Biology Center (QBiC). On day 1 of the AC meeting, the RIKEN
Executive Director Dr. Koyasu and the BDR Director Dr. Nishida gave an overview forRIKEN and BDR activities, respectively. On days 2 and 3, all PIs of BDR (divided intothree groups) were reviewed by the AC. Progress reports and future plans were provided
in the advance documentation, and each PI gave a summary presentation andresponded to questions from the AC. On days 3 and 4, the AC had a closed discussion
and drafted the report and recommendations. The AC had a further discussion with theDirector Dr. Nishida. Finally, the AC chair summarized the AC reports andrecommendations to BDR PIs with Dr. Koyasu in attendance. Here the Chair and Vicechair have summarized their AC panel members’ reflections and recommendations.

1. Evaluate (1) whether the center’s research meets international standards and isregarded as world-leading, (2) whether its research results have contributed tosociety, (3) and whether its up-to-date activities and strategies meet the aims of
RIKEN’s fourth mid- to long-term plan (7-year plan).
BDR aims to establish life science that contributes to the extension of the healthy lifespan,
which appropriately covers broad fields of biology. The AC enjoyed the PIs’ reports andpresentations, which overall are at an international level, with some being world-leading.
Many senior PIs are international authorities, while most junior PIs are leading newtalents for their fields. Some examples of the strikingly outstanding senior PIs are H.
Hamada (Organismal Patterning), M. Ueda (Cell Signaling Dynamics), C. Furusawa(Multiscale Biosystem Dynamics), K. Takahashi (Biologically Inspired Computing), T.
Kitajima (Chromosome Segregation), Y. Okada (Cell Polarity Regulation), Y. Watanabe(Pathophysiological & Health Science), T. Tsuji (Organ Regeneration), H. Ueda(Synthetic Biology), S. Hayashi (Morphogenetic Signaling), and F. Matsuzaki (CellAsymmetry). Examples of the most talented junior PIs that we interviewed include M.
Morimoto (Lung Development & Regeneration), I. Hiratani (Developmental Epigenetics),and Y. Wang (Epithelial Morphogenesis).

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Furthermore, some of the research results are close to translation for wider impact thanin academic science alone. Examples include methods for generation of hair follicles,
pituitary, salivary, and skin having hair and sebaceous glands from iPS cells, alreadysupporting advancement to clinical trials (T. Tsuji), promising translational molecularimaging validations in rodent models before applications in human subjects (Y.
Watanabe), and rational epigenetic drug design with delivery of candidate molecules
targeting LSD-1 (T. Umehara). However, the panel wishes also to emphasise the equallyimportant contributions to society from conceptual advances in basic research provided
by RIKEN scientists. Some highlights include structural snapshots of nucleosometranscription by RNA polymerase (S. Sekine), explorations of evolutionary dynamics (C.
Furusawa), the structural basis of translation initiation under diverse stresses (T. Ito), AIintegrated automated in-cell single molecular imaging system (M. Ueda), and 3D
genome-wide structure (Y. Taniguchi).
All of the projects align well with at least one of the aims of the 7-year plan. More than
300 papers are published annually in international journals, including some in the highest
impact journals such as Nature, Science, and Cell. Each of the predecessor centers
was already recognized as a world-leading center in their respective fields; the AC isconvinced that BDR soon also will be internationally recognized as a world-leadingcenter.
In addition to the above research, BDR delivers wider benefits to society. BDR supports
generation of transgenic mice for many laboratories not only in Japan, but also in othercountries. This is a valued resource for researchers in many biological fields. BDR also
is actively engaged in outreach activities. In 2018, BDR held three Open House activities,
and more than 6,000 people visited BDR. Furthermore, BDR organized workshops forhigh school teachers and students and received 95 visits from school students anddelegations. These are important public engagement activities that will educate andencourage the next generation to become involved with and use science responsibly.
To achieve RIKEN’s fourth mid- to long-term plan, center-wide projects were launchedunder the leadership of the BDR Director Dr. Nishida. This is a new funding scheme thatshould provide incentives for productive collaboration among researchers not only in
BDR but also outside BDR. To date, two projects, the Organoid project and the DECODEproject, have been launched. These projects have the potential to facilitate productive
collaboration among researchers that used to belong to three different centers, but thiswill need explicit implementation plans and careful monitoring. The Organoid project has
fostered development of a new collaboration with Cincinnati Children’s Hospital, which
promises to make BDR research more visible to biomedical researchers internationally.
The AC strongly supports the Director’s plan to launch additional BDR Center projects

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proposed by BDR PIs, which should promote further collaborations between researchers
who work in different locations. The AC strongly supports the Director’s plan.

2. Center director will present a SWOT analysis on the management of the centerto their AC. The AC is asked to evaluate whether the SWOT analysis and thedirector’s management proficiency are suitable.
The AC agrees fully with the analysis provided by Dr. Nishida. BDR was established bymerging three centers, CDB, QBiC, and CLST, in 2018. BDR has now more than 60 labs
scattered across Kobe, Osaka, Yokohama, and Hiroshima. Because of the distributed
locations and diverse research fields, it is challenging to integrate the new center in aharmonious way and to realise advantages from this merger. Despite these difficulties,Dr. Nishida already has shown strong leadership in joining strengths of the laboratories
to address three strategic aims: 1. Visualization of molecular and cellular states to enableprediction and control, 2. Multi-level analysis of organogenesis and inter-organrelationships, and 3. Regulation of life cycle progression. These will harness strengths
in BDR across the broad fields of biology, spanning from structural biology, cell biology,
and developmental biology to brain imaging and regenerative medicine.
The panel believes that these aims well capture the diversity and potential of BDR PIs.
Further, there was considerable evidence of collaborations within the BDR, with many
papers having multiple PIs as authors. This is excellent and will naturally encourage
innovation through cross-fertilization. However, a caution that the AC wishes to highlightis that efforts to align science do to risk realizing the outstanding potential of its individual
investigators; the AC feels that the research area for each PI should not be defined orconstrained too rigidly if creative science is to flourish. These aims will contribute to theefforts in extending healthy lifespan, which is a major concern for Japan’s rapidly aging
society. The center projects launched by Dr. Nishida also offer a great opportunity forhighly committed, excellent scientists with various expertise to collaborate with eachother to achieve greater impact. Furthermore, the opportunity that BDR affords for an
exclusive focus on research with no distractions (other than contributing to themanagement of core support structures), complete independence (even for the juniorPIs), good resources, and excellent core support in specific areas such as microscopy
and mouse unit are strong points for BDR. Additionally, BDR is supporting its early career
researchers; both students and postdocs emphasized the excellent training that theyreceived from their mentors. Director Dr. Nishida thus has set appropriate strategies andcreated an environment in BDR allowing its researchers to work efficiently. Nonetheless,the panel noted areas in which the effort could be improved. To complement the work ofindividual investigators focused on methods, such as Nikaido, it would be desirable toinvest further in core support for genomics, that could deliver cutting edge, advanced3

genomic methods unavailable commercially, and with the ability to deliver uniqueobservations for all laboratories. The electron microscopy and sequencing facilities are
not at the level that an institute such as BDR deserves and should be strengthened. TheAC strongly encourages BDR to develop and implement an actional roadmap andleadership position (can be a part time appointment) to achieve rapid growth anddevelopment of robust cryoEM workflow as a core facility.
The institute has a number of unique opportunities to further distinguish itself
internationally, e.g., by promoting many more links between the live imaging andorganoid/developmental groups. Specifically, the imaging capabilities enableassessment of metabolic function, oxygenation, cell type composition, and linkage oftransplanted tissue to the host vascular system in real time. Few or no other stem
cell/developmental biology institutes are in the position to perform these assessments.
Initiation of a new programme of “mini-grants” dedicated for collaborative projects, would
also open for postdocs and students, could help to encourage such integration further.
An apparent problem for the merger is the dispersed nature of the institute, with itsconstituent sites being so far apart. This makes it difficult to preserve optimally productive,
day-to-day communication. The regional dispersion threatens to undermine thedevelopment of BDR into a coherent, leading research institution. The AC feels that theturnover of faculty in the next few years offers an opportunity to begin to consolidate theinstitute at a single site on the Kobe campus. While appreciating the logistical challenges,
the AC views this as an important move for the long term competitiveness of the instituteat the international level. The planned new Projects could aid this process.
A guesthouse or overnight accommodation for international visitors, students, andcollaborators at each site would contribute to addressing this issue. However, even in
the same center, the panel believed that there were insufficient opportunities for people
to meet and socialize in ways that would enhance productivity. A central venue whereeveryone working in a site could interact informally, like a cafeteria or common room, will
be desirable. In addition, because of a large number of labs in BDR, the panel weredisappointed to learn that the retreat does not accommodate the entire staff. Thishampers joint visibility of research and interactions of researchers. All researchers
should participate in a centre-wide retreat at least once every two years.
The panel felt that opportunities for students and postdocs to regularly present theirresearch in English, and for mentoring and career training of junior faculty, postdocs,staff scientists, and students, should be increased . An essential additional componentof developing early career staff would be strengthening the mechanisms by which senior
PIs mentor junior PIs, postdocs, and students. Thus, regular meetings of PIs with their4

mentors should be mandatory, even when the perception is that no apparent problems
exist. Such meetings should continue throughout the term of appointment of the juniorfaculty. Seminars and workshops focused on challenges of career development,
increasing formal training offerings in how to write and present research proposals also
are important, particularly for junior PIs coming from overseas. It also would be importantto support all PIs to establish clear identities for themselves by focusing on a limited setof related biological problems rather than studying many topics superficially. Regular
joint progress reports to encourage feedback would be helpful for all. We encourage theRIKEN administration to find ways of accessing funds to support the salary and tuitionof international students.
As Director Dr. Nishida noted, the diversity of personnel is limited in BDR and should beimproved. For recruitment of more women, provision of extensive daycare for children
would make the institute attractive, and this would need to be made widely known if
women are to be recruited successfully.
Another area in which diversity and internationality could be improved is graduate
training. With its excellent resources and international outlook, BDR could run a “flagship”
international PhD program in partnership with universities (IPA), which could attract anddevelop talented young scientists from overseas (an initiative that should not conflict with
the independent missions of Japanese universities). A current IPA program offers only
3-year fellowship but should cover 5 years for students from outside Japan. This program
also needs to be made widely known, which may eventually improve the diversity of BDR
researchers and help BDR be recognized as an international PhD training center.
The panel appreciated that one of the greatest impending problems for BDR is that manylabs will be closed in 2023. This should be clearly notified to all these lab members, andthe relevant researchers should be encouraged to apply to positions well before 2023.
To move to next positions in universities, external funding and education experiences
are important, and BDR should support the affected researchers. Maximal transparency
and timelines in communicating decisions from the Senior Management Committee
regarding tenure and new recruitments is highly desirable.
The BDR could benefit from more autonomy from the central RIKEN administration in
the ability to determine its tenured faculty decisions.
Finally, the panel wishes to highlight what a big loss Dr. Masayo Takahashi’s recent
departure form BDR was. Her work is exemplary in demonstrating a path from basic
science to regenerative medicine. The panel believes that the work was very importantfor BDR as an example of world-class translational research. To this end, BDR shouldeven more aggressively seek opportunities to bridge its excellent basic science with5

clinical research in neighboring hospitals and universities.

3. Evaluate whether the center’s initiatives on the items given below have resulted
in improvements and recommend further measures to be implemented by thecenters.
● RIKEN is conducting a program to enhance its function as the coreorganization for research partnerships, which we refer to as the “Science andTechnology Hub.” The AC is asked to evaluate the center’s achievements incollaborative activities, including those belonging to the Science andTechnology Hub.
● Initiatives on the internationalization of the centerBDR currently has 150 domestic and 12 overseas collaborations. In addition, BDR has
close collaborations with several universities, institutes, hospitals, and companies. By
promoting the Organoid project, BDR launched a joint lab in Cincinnati, which will help
BDR research to be more visible internationally. BDR also organized highly successful
annual symposia, joint meetings, and many seminars. Furthermore, BDR supports manylabs in Japan and other countries to generate transgenic mice, and this is a valued
activity for many biology fields. BDR therefore makes an enormous contribution to theglobal visibility and reputation of RIKEN and is widely recognized as a “Science andTechnology Hub.”In BDR, foreign researchers are well supported. However, communication being mainly
in Japanese remains a barrier to their full integration. It also hinders the Japanese
students from learning English to present their results and function in an internationalenvironment. Strong efforts must be made for the institute to become more attractive forforeigners. This could include, for example, generous funding for short-term visits ofinternational experts, funds for visiting students and postdocs etc. All of these would
require aggressive promotion of such opportunities.

4. Evaluate (1) whether each of the PIs fulfill their duties in accordance with themission of the center, taking into consideration the 7-year plan; (2) whether theirresearch meets international standards; (3) and whether they have suitablecapability on the laboratory management, including their efforts to support earlycareer researchers.
Note: For item (2), please refer to the Addendum for the suggested points to be evaluated.
The evaluation of each PI is presented separately, but the AC was impressed by thehigh-quality research conducted at BDR. All PIs are making their research meet the6Center’s mission, but it is important that their research should not be re-directed too
rigidly. Most of their research meets international standards, and most PIs seem to havesuitable capability on the laboratory management. However, as noted above, formal
support mechanisms for early career researchers at the senior postdoc and researchscientist level currently are weaker than at many other institutions, (e.g., lack of specifictraining opportunities for soft skills such as grant writing, etc.). The strongly positive
sentiments that the panel heard from early career researchers, postdocs and students
provides a strong substrate for improving this.

Members of the BDR Advisory Council
Ryoichiro Kageyama, Kyoto University (Chair)
Maria Leptin, European Molecular Biology Laboratory/University of Cologne (Vice-Chair)
Martin Fussenegger, ETZ Zürich and University of Basel
Christer Halldin, Karolinska Institutet
Makoto Higuchi, National Institute of Radiological Sciences
Midori Kamimura, Teijin Institute for Biomedical ResearchPaul M. Matthews, Imperial College London
Hiromitsu Nakauchi, Stanford University/The University of Tokyo
Masaki Sasai, Nagoya UniversityMichael Sheetz, National University of Singapore
Cliff J. Tabin, Harvard Medical School
Soichi Wakatsuki, Stanford University
Yoshihiro Yoneda, National Institutes of Biomedical Innovation, Health and Nutrition
Kenneth S. Zaret, University of Pennsylvania

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