Advisory Council ReportonRIKEN Quantitative Biology Center (QBiC)

November 2013

1Meeting Program
The Advisory Council (AC) of the RIKEN Quantitative Biology Center (QBiC) met in Kobe fromNovember 24-27 to discuss the progress and scientific directions of this new Center(established April 2011). The meeting opened with a tour of OLABB in Osaka and visits toindividual laboratories. Following the return to Kobe, RIKEN Executive Director Dr. Maki
Kawai summarized the history, current missions and organization of RIKEN. She drewattention to the Terms of Reference from the President Noyori to the ACs of each Center,
including specific points relating to the management policy of the QBiC (see Appendix).
The QBiC Director Dr. Yanagida gave an overview of the QBiC. He described the overall
mission of QBiC, which is to model whole cells so as to predict and control living systems. He
outlined the organization of the Center. He presented QBiCs 10-year roadmap comprisingfour steps: quantitative measurement, modeling and design; the elucidation of common
principles; the prediction of systems behavior; and, finally, the control of systems behavior.
Further information about the overall goal of QBiC and the individual investigators wasincluded in a White Paper, copies of which were distributed to the AC before the meeting. Dr.
Yanagida also presented his own terms of reference for the AC (see Appendix).
The specific research topics were presented on days 2 and 3. Following an introduction by
QBiC Deputy Director Dr. Taiji, the AC heard presentations on the main research topics - cell
polarity, differentiation, techniques, structure and design. The presentations were made by up
to three group leaders and there was ample time for discussion. On day 2 there were two
short presentations on collaborative research, and an evening poster session summarizing
work from each of the labs. Formal presentations were concluded on the afternoon of day 3
with an overview of QBiCs Future Plans led by Team Leader Dr. Takahashi, with participationfrom several of the group leaders, and lively discussion with the AC. Overall, the writtenmaterials, presentations and posters were of the highest quality.
Ample time was available on the afternoons of days 2 and 3 for internal discussions of theAC. On the morning of day 4, the AC drafted its report on the Center and evaluations of theindividual groups. Afterwards, the AC presented its report and recommendations to Dr. Kawai,
Dr. Yanagida and the group leaders.
During the review, the AC met only with group leaders. The AC recommends that in future
it meet with representatives of the graduate students, postdoctoral fellows andresearch scientists to enable the AC to evaluate the scientific and working environment forjunior researchers.
2Summary
QBiC is a highly interdisciplinary Institute at the interface between biology, engineering andphysics. It focuses on developing new, quantitative approaches to biology—especially throughsingle-molecule and single-cell techniques, together with systems theory. This research topic
is timely and should significantly strengthen biological research in Japan. Despite being only
2.5 years old, QBiC has established a state-of-the art infrastructure with technologicaldevelopments at the highest international standards. The institute has clear direction fromstrong management. There are many collaborations both within and outside of RIKEN, andinternationally.

Progress
Given that QBiC has only been operating for 2.5 years, progress towards meeting the longterm goals has been excellent. QBiC has already established itself as a world-class Center for
quantitative measurement, modeling and design.
1. Microscope development takes place in several laboratories. This concerted effort is not
redundant, but rather the concentration brings QBiC to the very highest international level.
There is a high level of innovation, which is evidenced, for example, by patent applications. To
complement the new microscopes, such as the new light-sheet-based single-molecule
microscope and the ultrafast super-resolution microscope, there has been considerable effort
in image processing and the development of new imaging tools. What is particularly
impressive is that technical contributions are being made by several labs, indicating that theenvironment is supportive and collaborative.
2. There are several theory and simulation groups. This effort ranges from atomic modelingthrough to single-molecule modeling, the modeling of network behavior, and the beginning ofwhole-cell modeling. The Center takes advantage of its close ties with the K supercomputer.
3. Advanced tools in molecular and cell biology - mass spectrometry, molecular genetics andmicro-devices - are also ground-breaking and at the highest international level. Particularmention is made to single-cell metabolomics, CMOS chips and new site-specific genemanipulation and knock-out tools.
4. There is close collaboration between theorists and experimentalists. It is particularly
noteworthy that the stem-cell dynamics project is led by a theorist who has enlisted the help ofexperimentalists to test his hypothesis that “stemness” is associated with oscillatory network
behavior.

3The presentations clearly demonstrated that the combination of experiment and theory has
already led to major discoveries. These include
1. The role of molecular number fluctuations in the dynamic variation of polarization during
cell motility, and the potential roles of these fluctuations in the searching strategies oflocomoting cells.
2. The role of feedback between motor activity and microtubule state in the dynamic decisionmaking process by which a neurite differentiates into an axon.
3. The role of network dynamics in determining the states of stem cells, and the measurementof fluctuations in stem cell transcription factors during early mouse development.
4. The roles of network dynamics in circadian rhythms.
Despite the relative newness of the Center and the fact that some of the groups have only justset up their labs, there was a feeling from the AC that some of the groups had not publishedas much as they could have. With the infrastructure established and exciting results now
being produced, the AC recommends that increased emphasis be given to thepublication of high-quality papers and the dissemination of the results at international
meetings.
Support from external grants is generally strong, another indication that the Center is
progressing well in its early phase.

Objectives
The roadmap (2011-2020) vision of Dr. Yanagida was clear and most investigators are onboard. Indeed, it was remarkable how often the same themes recurred in the different
presentations. The long-term goal is whole-cell modeling to be achieved through four steps:
quantitative measurement, modeling and design; the elucidation of common principles; theprediction of systems behavior; and, the control or steering of systems behavior. Two themes
are prominent: the bridging of scales (reducing dimensionality) through the study of systembehavior, and the role fluctuations (yuragi).
With respect to achieving these goals, it is clear that the first two are progressing well: thequantitative measurement, modeling and design and the elucidation of common principles.
The AC feels that despite this progress it is very important to really “nail” the finding that havebeen already made - for example, that molecular number fluctuations play a fundamental rolein variation in dynamic behavior. Therefore, the studies should not move too quickly to theprediction and control phases. Likewise, the development of new techniques should not beabandoned.
4The AC felt that it in order to be successful in the control phase of the objectives, it was going
to be necessary to focus on a limited number of systems. The committee suggests that theCenter choose three areas - such as the immune system, stem cells and the brain - to focus
on. One strategy would be to bring several QBiC group leaders to collaborate in each of theseareas. The AC recommends that QBiC recruit three additional team leaders to bring in
biological expertise to the projects. In this way, QBiC can be in the driver’s seat with theseprojects (rather than playing secondary roles to outside collaborators). These projects would
constitute a “strike zone” and maximize the chance of making a truly huge impact, i.e. a homerun. The hiring of these new groups will require additional budget support and space.

Fostering young talent, diversity and internationality within QBiC
It is highly commendable that 40% of the group leaders were recruited while in their 30’s. Thisno doubt contributes to the innovation, collaboration and general excitement within theCenter. However, given that most positions in RIKEN are of limited duration, it is especially
important that these groups are given advice from their senior colleagues to prepare them for
future positions in academia, research or industry. Therefore the AC recommends
establishment of a mentoring program for unit and team leaders. For example, a groupof more senior group leaders including the Director and a group leader not closelycollaborating with the unit or team leader, provide periodic advice on publications, grants,personnel management and ultimately help with job applications.
To increase the internationality, the AC recommends that QBiC establishes anInternational PhD program, for example modeled after the IMPRS of the Max Planck
Society. Key aspects of this program are international advertising, common recruitment
mechanism for all labs, on-campus interviews of short-listed candidates, a minimum of 50%
foreign student intake, an international office to help moving to Japan (apartments, banksetc.), and student organized events such as special lectures, retreats, opportunities todevelop soft-skills such writing manuscripts, making presentations, and applying for grants.
To bring in the top postdocs and foster collaborations, especially between experimental andtheory groups, the AC recommends the establishment a Postdoctoral Fellows program
modeled after e.g. the Lewis-Sigler program at Princeton, the Bauer program at Harvard orElbe program at MPI-CBG in Dresden, Germany.
The gender diversity of QBiC is very low with only one female group leader. The ACrecommends that more female scientists be recruited at all levels. This requires
5concerted attention from upper management including the Director of the QBiC and theRIKEN administration. We were disappointed that this subject was not addressed in theopening presentations and no data was made available to the AC about the numbers offemale scientists in QBiC. Attention should be given to practical issues such as child care andfamily leave.

Maintaining and improving diversity of approaches, fostering collaborations
There are a strong collaborations within QBiC, with other institutes inside and outside RIKEN
and also international collaborations.
One difficulty identified by the AC is that the Center is split between several sites. This makes
collaborations difficult. To facilitate collaborations within the Center, the AC recommends
that additional space be made available adjacent to the new building at OsakaUniversity.

Budget and other issues
The Center is strongly supported by RIKEN administrative staff, and the AC strongly supports
the maintenance of this level of support.
Technology transfer is important for an Institute developing new techniques and should be apriority for QBiC and RIKEN. The AC were unable to evaluate the procedures for technology
transfer. The QBiC Director and the RIKEN administration need to make sure that appropriate
and effective measures are taken in this regard.

Summary of recommendations
1. The AC recommends that additional space be made available adjacent to the new buildingat Osaka University.
2. The AC recommends that QBiC recruit three additional team leaders to bring in biologicalexpertise to the projects.
3. Now that the QBiC has successfully established itself, the AC recommends that emphasis
now be given to the publication of high-quality papers and the dissemination of the results atinternational meetings.
4. The AC recommends the establishment of a mentoring program for unit and team leaders.
6

5. The AC recommends that more female scientists be recruited at all levels.
6. The AC recommends that QBiC establishes an International PhD program
7. The AC recommends the establishment a Postdoctoral Fellows program.
8. The AC recommends that in future it meet with representatives of the graduate students,
postdoctoral fellows and research scientists.
Jonathon Howard
Chair of the Advisory Council
8 December 2013
Advisory Council Members
Jonathon Howard <howard@mpi-cbg.de>David A Case <case@biomaps.rutgers.edu>
Martin Fussenegger <fussenegger@bsse.ethz.ch>
Makoto Suematsu <gasbiology@z6.keio.jp>
Shigetada Nakanishi <snakanis@obi.or.jp>
Takao Kondo <kondo@bio.nagoya-u.ac.jp>
Masaki Sasai <sasai@tbp.cse.nagoya-u.ac.jp>

7Appendix: Terms of ReferenceTerms of reference (QBiC)
Direction of QBiC
Objectives 2011-2020
Progress
Fostering talent and diversity within QBiC
Recruiting young talent
Maintaining and improving diversity of approaches
Current collaborations within RIKEN, Japan and internationallyTerms of reference (President)
Up to international standards?
Management policy
roadmap
attracting top international talent
personnel turnovercollaboration inside and outside RIKEN (including globally)
RIKEN Missions (Dr. Kawai)
Strategic, problem-solving research to meet national and social needs
Develop, maintain and share state-of-the-art infrastructureInterdisciplinary research
Collaboration within and outside RIKEN for industrial and medical applications
Training outstanding scientists

8