Vol.3 No.1 2010

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Research paper : A bioinformatics strategy to produce a cyclically developing project structure (M. Suwa et al.)−8−Synthesiology - English edition Vol.3 No.1 (2010) We already possess all olfactory receptors in SEVENS. We believe we can conduct a response simulation of all olfactory receptors against odor molecules by modifying GRIFFIN.5.2 New research phase of GPCR It is necessary to consider the recent rapid advancement in the research on the 3D structure of GPCR. For a long time, the only protein to have its 3D structure deciphered was bovine rhodopsin, and this was used as a mold of the model structure to be analyzed, as a matter of fact, in drug discovery research. However, in 2007 to 2008, the GPCR structures of different families[14][15] were determined one after another, and the conventional research method is expected to change rapidly. From the new 3D structure, it was found that the differences in the structures of the ligand binding site and the G protein binding site were spread out and could not be ignored between families. It was indicated that it is necessary to determine the 3D structures of all major GPCR families as molds. However, such immediate structure determination is quite difficult as both expression and crystallization have become bottlenecks. Therefore, structural information must be obtained through a different approach from the 3D structure determination. It is important to extract and overview the information that reflects the 3D structure for each family at sequence level, and SEVENS can be used for this very purpose.5.3 Development of an integrated database Although the databases containing bioinformation are the foundation of the life science research, their utility is low since they are scattered around in various research institutions. Therefore, the government is working on a system for integrating and managing the various DBs (for example, the Integrated DB Project of MECSST and Ministry of Economy, Trade and Industry). In the future, SEVENS must be designed for such integrations. It is necessary to take measures to completely automate updates for permanent maintenance and management, and yet maintain high data reliability. 6 Discussion6.1 Research scenario: Cyclically developing Project structure The results accomplished and the future developments of the Project were presented in the above chapters. It was stated earlier that it is difficult to write a “correct” research scenario into the far future since the advancement of research in the life science field is quick. Yet in retrospect, I think the research developed extremely efficiently. The Project started in 2000, and the first phase of Full Research was from the development and publication of the comprehensive DB of GPCR. However, this phase was the “hop” (Type 1 Basic Research) of the larger research development phase, and this was followed by the cyclic development of joint research in the manner of Type 2 Basic Research, joint research in the manner of Product Realization Research, and continues to the present (Fig. 5(a)). Why did it take such a development form rather than being linear? One could think of the following reasons. First, as described in chapter 2, the time needed for results is short in the bioinformatics fields, and each research phase of Fig. 5(a) tends to be small projects that are resolved in 1~2 years. Considering such small-scale research directions as small vectors, the vector that is synthesized from those small vectors and the direction of life science in its entirety determines the direction of the whole project. The determination of the direction is accomplished at each phase. Next, since the direction of the life science field moves in cyclically developing manner together with dramatic technological development, it will continue to develop under such influence. What was the driving force that propelled these small vectors without interruption to the present? Following is a list of the factors, and I think these worked as shown in Fig. 5(b) to determine the direction of research. 1) Core technology matured over a long-termOver 8 years were spent on the Project. Normally, a project spans over about 5 years, and orders to stop the research could have been given at any time. However, in our case, the stage of research continued to rise through the long-term maturation of the core technology. The essential factor that prevented the interruption of the cyclically developing structure is the fact that SEVENS itself won trust by diligently building up improvements in gene identification pipeline, DB, and program. While there are many DBs that are completed, written up in a paper, and are never maintained afterwards, the fact that SEVENS is updated in accordance to the demand of the moment has become a brand power, and I think this is the reason we are getting offers for joint researches. 2) Close collaboration with experimental researchersThe bioinformatics technology is able to process large amounts of data in a short period and produce results. However, whether the results are meaningful or not must be demonstrated in experimental research. By obtaining feedback of the demonstrated results, the parameters set in elemental technology can be modified to move in a better direction. On the other hand, the experimental researchers can use the predictions to modify their experimental system to one with lower risk and cost. In our Project, we discussed extensively with experimental researchers through various joint researches. Feedback in both directions occurred several times, and the improvements of analysis and

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