April 22, 2010
RIKEN Harima InstituteResearch Promotion Division

Report on Structural Physiology Research Group Midterm Review
Laboratory Leader: Group Director, Atsuo Miyazawa (D. Sci.)
Date: Friday, February 12, 2010
Venue: RIKEN Harima Institute（SPring-8）
Reviewers:
Prof. Masayoshi Nakasako（Faculty of Science and Technology, Keio University）
Prof. Makiko Suwa（Computational Biology Research Center, National Institute of Industrial Science andTechnology）
Prof. Keiichi Namba（Graduate School of Frontier Biosciences, Osaka University）
Prof. Yifan Cheng（Biochemistry Department, University of California, San Francisco）

Abstract of the reports:

REVIEWER 1
The Structural Physiology Research Group aims to study structures and functions of a number ofbiologically very important protein families, such as membrane channels, etc. To achieve its scientificaims, a number of novel technologies are developed, such as molecular labeling by metalloprotein-tagand GFP-pipeline for eukaryotic membrane protein expression and crystallization. Such technology
developments are very impressive and will have application potential in a much broader field of structuralbiology. Selection of Team leaders was excellent. All team leaders have excellent track records andvarious backgrounds. There are coherent and synergetic activities of the Teams, which promote
excellent scientific environment. There are also a large number of collaborative projects between theTeams. Overall, the Group is very well equipped and positioned to tackle difficult and important biologicalquestions. The research group has made significant progresses in the past four years, and all teams arewell positioned to continue their efforts outlined in their future research plans. Continued support to thegroup is necessary and important.

REVIEWER 2
1. On the consistency of the Group’s mission and the RSC’s mission
The RSC has missions on the scientific researches through utilizing X-rays provided from the SPring-8
and the X-ray Free Electron Laser (XFEL) facility. While the Bio-multisome research team seems to pay
little attention to the RSC mission, the other research teams have missions match with the RSC’s.
2. On the research objectives
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The research objectives are unclear and difficult to understand probably because of the less organizedresearch teams.
3. On the research results
The number of publications, which include significant contribution from research teams, is a few,
despite a large budget has been given to the group. Among the four teams, this tendency is particular in
the Bio-multisome research team. On the other hand, the Actin-research group showed the outstanding
activity by the Nature paper. The group also contributes to the utilization of SPring-8 regarding the fiber
diffraction method.
4. Management of the Research group
The group leader seems to abandon his important duty, the management of the four research teams in
the past three years. Thus, it will be better choice for the RIKEN to recruit a new project leader who canbe more responsible for the management of the research project.
Group member composition
The four research teams works independently, and the research group looks like an assembly of
university laboratories. Despite the scientific achievement of the Actin-group, the number of researchers
is too few.
Researchers’ interaction
Young researchers and graduate students communicate well between the different research teams
and discuss their research regarding the methods to prepare samples.
Facilities and equipments
Facilities and equipments of the research group are sufficient to carry out their research plans.
5. Future research plans
Except the Bio-multisome research team, the three research teams have plans to utilize effectively theSR and XFEL facilities. But, their plans are better to be reevaluated by scientists more professional inutilizing the facilities.
6. Possibility of cooperation with related fields
To improve the activity of the Bio-multisome research team, the research team may be better tocollaborate with a scientist, who contributes to EM science field more significantly.
7. RIKEN’s management
The Bio-multisome research team provides their equipments to an NPO organization. The equipments
are given for their scientific activity not for their NPO activity. The project reader should consider thispoint deeply, because the budget for their research is provided from tax. Could the RIKEN stop theaction? The management of the equipments would be discussed after the termination of the research
project.
The budget from the RIKEN is given unevenly to the research teams. After the evaluation of the abilities
and activities of the research teams, the RIKEN can supply the budget depending on their scientificactivity.

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REVIEWER 3
1. Research Objectives: novelty, specific significanceThis group intends to elucidate a dynamic physiology from three dimensional structure analyses ofproteins and complex by the total fuse of an X-ray crystallographic analysis and an electron microscopy.
This group is very unique without being found elsewhere in the view point that they are performing thegeneral development/ application in the environment where high-performance machinery is prepared.
Therefore a feeling of expectation from the outside for this foothold seems very large.
2. Research Results: Originality, specific significance social impact
Four teams in this group gave us extremely superior results. 1) Bio-multisome Research Teamdeveloped the precise label method and structure analysis technology with a scanning electron
microscope (SEM). 2) Three-dimensional Microscopy Research Team focused on the transporter
proteins and constructed the system which settled methodology of ranging as one package from atwo-dimensional crystal to structure determination. 3) Molecular Signaling Research Team founded theexpression condition of the taste receptor. In addition, they developed the high-throughput screening
technology using the GFP. 4) X-ray Structural Analysis Research Team determined the structure of Actin
filament and analyzed the dynamics of it. Each result is superior contents which lead the world. The
social ripple effect of these results seems very large, since these researches have large difficulty though
they are strongly required.
3. Management of the Laboratory: Laboratory member composition, researchers interaction facilities andequipment etc.
They gather excellent talented people individually from various fields and become the very uniquegroup. Dr. Miyazawa the leader of this group respects the individuality of each team leaders and he does
not show overall directionality in "intentional". It is surely pushed forward an original study without alimitation, judging from the researcher side, and this policy produces ideal environment and has thepossibility that very large result is provided.
But it is possibility and the hair's breadth that project ends after several years being spent by only
finding the condition for structure determination. In addition, I am sorry that it could not see the synergy
effect that all these talented people gathered in one foothold.
The equipment parts are enough with the highest devices which the purchase is difficult foruniversities and for the other research institutes. Therefore it is necessary to be aware that result ofStructural Physiology Group is seen for a feeling of over expectation from the other groups.
4. Future research plans: possibility of cooperation with relates fields etc.
It seems that the future plan of this group is to promote more the individual themes in each team. Such
directionality is too enough in the case of university because the output of individual study is splendid.
However, I think that they cannot make use of the advantage enough, that they formed a group with thelimited term (7 years). I hope they show the synergy effect of inter group cooperation by confirming thepresent progress in a road map described strategically.
5. Overall assessment
Very excellent talented people are gathered from various fields. The administration of the whole group3

respects the independence of these individual researchers and does not show, definitely, thedirectionality as the whole group level to "intentional".
This administration succeeds for the individual team, and superior result is provided. In addition, thecommunication of leaders and the young researchers is planned well in the good environment. This
environment is too enough if there is that of the university. But a feeling of expectation from the outside
for innovative techniques is unexpectedly large for the research facility where all these latest facilities
were covered all.
Therefore there will be the necessity to exhibit the result as the group whose term was limited.
I hope they show the synergy effect of inter group cooperation by confirming the present progress in aroad map described strategically. For example, I think it is one of directionality that they choose theprotein the structure of which is determined for the first time only when their technology is joined.
6. Other opinions: RIKEN management, RIKEN’s review systems etc.
RIKEN’s review system is well designed according to its Mission of RSC. As well as the presentationof the research, I thought the direct interview to researchers to be a good system.

REVIEWER 4
Since its start in April 2006, the aim of Structural Physiology Research Group is to gain physiologicalunderstanding on the mechanisms of biomolecules and their complexes, such as membrane andcytoskeletal proteins, as to how they work in the cellular activities, from the structural view points. The
four team leaders recruited to start this ambitious 7-year project are those who have expertise inthree-dimensional electron microscopy of biomolecules and cells, X-ray crystallography of biomolecularcomplexes, and X-ray fiber diffraction analysis of fibrous assembly of biomolecules. Their research
themes include many important topics in biology, from cellular signal transduction, ion transport, andmotility to neural signaling.
In spite of the diversity of the research topics they chose to work on, the team leaders aimed to sharenot only the equipments and expertise but also ideas for the development of new experimentaltechniques as well as for the interpretation of data to gain insights into the mechanisms as much anddeep as possible, by encouraging daily communications between the members of the teams over theteam boundaries. I think it is a great idea and appreciate the continued effort of the four team leaders toachieve their goals. I hope that each member of the group as well as each of the team leaders will keep
his/her active communication with people around as much as possible and continue and further expand
their collaborative studies.
The overall activities of the group appear to be good considering the difficult challenges that eachteam is facing. Although the productivity may not look so great in terms of publication at this moment
after four years of the project term, it is not surprising because the goal of each team is set at anextremely high level and also requires the development of new experimental methods that are not soeasy. I am sure that all the teams will achieve what they aim for within a couple of years to come. The
midterm reports by the four teams actually show promising progress.
4For some reason, which is probably to do with how the group started its initial activity, the financial
resource is unequally distributed among the four teams. Now, since Group Director Dr. Miyazawa got an
appointment as professor and the laboratory at University of Hyogo, which gives him more opportunities
to seek other funding sources, it may be wise to make some changes in the arrangement of how thefinancial resource be distributed to allow the other three teams to have more capacities in managing
their own team’s research activities.
As I mentioned in my summary remarks of the review that I gave orally after the sessions of theMidterm Review held at RIKEN SPring-8 on February 12, the coordination of the efforts by the four
teams may be further improved. I understand that some collaborative studies by the joint effort ofmultiple teams are being carried out. But when each team leader gave an oral report in the review
session on the progress made so far by the team and the prospect for the remaining term, theirpresentations tended to sound like they are individual, independent work. Since all the research projects
that are being carried out in the group are all related to the biological functions of membrane andcytoskeletal proteins involved in signal transduction, ion transport, and cell motility to neural signaling,even the present research activities of the group can be presented as an integrated approach that
focuses on some of the important aspects of the cellular activity and may well be reorganized to actually
integrate them into more coherent collaborative studies. More cohesive efforts by the four team leaders
towards more highly integrated research projects would be appreciated.
Convergent use of X-ray diffraction and electron microscopy is one of the most powerful tools instructural biology to decipher the mechanisms of complex biological functions that are driven by large
macromolecular assemblies and cellular organelles. Since this group has the intrinsic capacity andpotential to make full use of this tool and develop the method further to make it even more powerful, theexpectations of the research communities of structural, molecular and cellular biology are not at all trivial.
I hope this group will become one of the international leaders in the field.

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