平成 22 年 4 月 22 日
独立行政法人理化学研究所
播磨研究所

構造生理学研究グループ

構造生理学研究グループ（宮澤研究推進部

中間レビュー報告

淳夫 グループディレクター）の中間レビューを下記のとおり実施いたしましたので報告いたします。

記【日時】平成 22 年 2 月 12 日（金）【場所】独立行政法人理化学研究所

播磨研究所【レビュアー】中迫雅由（慶應義塾大学理工学部

諏訪牧子（産業技術総合研究所
難波啓一（大阪大学大学院教授）

生命情報工学研究センター

生命機能研究科主幹研究員）教授）

Yifan Cheng (Biochemistry Department, University of California, San Francisco, AssistantProfessor)【評価結果の概要】

REVIEWER 1
The Structural Physiology Research Group aims to study structures and functions of a number of biologicallyvery important protein families, such as membrane channels, etc. To achieve its scientific aims, a number of novel
technologies are developed, such as molecular labeling by metalloprotein-tag and 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 structural biology. Selection of Team leaders was excellent.
All team leaders have excellent track records and various backgrounds. There are coherent and synergetic
activities of the Teams, which promote excellent scientific environment. There are also a large number ofcollaborative projects between the Teams. Overall, the Group is very well equipped and positioned to tackle
difficult and important biological questions. The research group has made significant progresses in the past fouryears, and all teams are well positioned to continue their efforts outlined in their future research plans. Continued
support to the group is necessary and important.

REVIEWER 2
1. On the consistency of the Group’s mission and the RSC’s mission1

The RSC has missions on the scientific researches through utilizing X-rays provided from the SPring-8 and theX-ray Free Electron Laser (XFEL) facility. While the Bio-multisome research team seems to pay little attention tothe RSC mission, the other research teams have missions match with the RSC’s.
2. On the research objectives
The research objectives are unclear and difficult to understand probably because of the less organized researchteams.
3. On the research results
The number of publications, which include significant contribution from research teams, is a few, despite alarge 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 can be 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 the SR and
XFEL facilities. But, their plans are better to be reevaluated by scientists more professional in utilizing thefacilities.
6. Possibility of cooperation with related fields
To improve the activity of the Bio-multisome research team, the research team may be better to collaborate witha 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 this point deeply, because
the budget for their research is provided from tax. Could the RIKEN stop the action? The management of theequipments 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 andactivities of the research teams, the RIKEN can supply the budget depending on their scientific activity.

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REVIEWER 3
1. Research Objectives: novelty, specific significanceThis group intends to elucidate a dynamic physiology from three dimensional structure analyses of proteins andcomplex by the total fuse of an X-ray crystallographic analysis and an electron microscopy. This group is veryunique without being found elsewhere in the view point that they are performing the general development/
application in the environment where high-performance machinery is prepared. Therefore a feeling of expectationfrom 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 Team developed theprecise 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 a two-dimensional crystal to structure determination.
3) Molecular Signaling Research Team founded the expression 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 whichlead 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 unique group. 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 a limitation, judging from theresearcher side, and this policy produces ideal environment and has the possibility that very large result isprovided.
But it is possibility and the hair's breadth that project ends after several years being spent by only finding thecondition for structure determination. In addition, I am sorry that it could not see the synergy effect that all thesetalented people gathered in one foothold.
The equipment parts are enough with the highest devices which the purchase is difficult for universities and forthe other research institutes. Therefore it is necessary to be aware that result of Structural Physiology Group isseen 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 the limited term (7 years).
I hope they show the synergy effect of inter group cooperation by confirming the present progress in a road map
described strategically.
5. Overall assessment
Very excellent talented people are gathered from various fields. The administration of the whole group respects
the independence of these individual researchers and does not show, definitely, the directionality as the whole3

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 a road map
described strategically. For example, I think it is one of directionality that they choose the protein the structure ofwhich 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 presentation of theresearch, 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 and cytoskeletal
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 in three-dimensional electron
microscopy of biomolecules and cells, X-ray crystallography of biomolecular complexes, and X-ray fiber
diffraction analysis of fibrous assembly of biomolecules. Their research themes include many important topics inbiology, from cellular signal transduction, ion transport, and motility to neural signaling.
In spite of the diversity of the research topics they chose to work on, the team leaders aimed to share not only
the equipments and expertise but also ideas for the development of new experimental techniques as well as for theinterpretation of data to gain insights into the mechanisms as much and deep as possible, by encouraging daily
communications between the members of the teams over the team boundaries. I think it is a great idea andappreciate the continued effort of the four team leaders to achieve their goals. I hope that each member of thegroup 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 each team isfacing. Although the productivity may not look so great in terms of publication at this moment after four years ofthe project term, it is not surprising because the goal of each team is set at an extremely high level and also
requires the development of new experimental methods that are not so easy. I am sure that all the teams willachieve what they aim for within a couple of years to come. The midterm reports by the four teams actually showpromising progress.
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 the financial resource be distributed to4

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 the Midterm
Review held at RIKEN SPring-8 on February 12, the coordination of the efforts by the four teams may be furtherimproved. I understand that some collaborative studies by the joint effort of multiple 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 andthe prospect for the remaining term, their presentations 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 ofmembrane and cytoskeletal proteins involved in signal transduction, ion transport, and cell motility to neuralsignaling, even the present research activities of the group can be presented as an integrated approach that focuseson some of the important aspects of the cellular activity and may well be reorganized to actually integrate theminto 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 in structural
biology to decipher the mechanisms of complex biological functions that are driven by large macromolecularassemblies and cellular organelles. Since this group has the intrinsic capacity and potential to make full use of thistool and develop the method further to make it even more powerful, the expectations of the research communitiesof structural, molecular and cellular biology are not at all trivial. I hope this group will become one of theinternational leaders in the field.

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