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Research paper : A systematic analysis of protein interaction networks leading to the drug discovery (S. Iemura et al.)−120 Synthesiology - English edition Vol.1 No.2 (2008) joined AIST in 2001. Visiting professor at The University of Tokyo, Kyushu University, and Tokyo Metropolitan University. Project leader of NEDO Chemical Biology Project since 2006. Completed Masters course at The University of Tokyo Graduate School. Life work is to pursue ultimate protein interaction research. In this paper, worked on development of direct nano-LC system.Discussion with reviewers1 On integration of elemental technologyQuestion (Noboru Yumoto)The originality of this paper is the success in integrating the elemental technologies including 1) construction of new system of liquid transfer, 2) improvement of analytical environment, 3) adjustment of analytical flow passage with minimum dead volume, and 4) optimization of sample preparation, toward the objective “to construct ultra high-sensitivity mass spectrometry system for protein network analysis.” Please explain 2), 3), and 4) as you did for 1), and how you achieved the objective by integrating the selected elemental technology.Answer (Tohru Natsume)The technologies for 2), 3), and 4) were basically accumulation of know-how and introduction of other technologies, and they were optimizations and combinations of existing technologies. I abbreviated them because they may sound like side stories. However, they may be important, as you indicated, so I added some stories taking care not to distract from the main theme of the paper.2 On relationship between research objective and societyQuestion (Hisao Ichijo)Research for problem solving is very detailed and convincing, but I feel there is some lack of “relationship between research objective and society” and “evaluation of result and future development.”I think it will be easier to understand if you add some description that the objective “to find pathogenic mechanisms and new drug discovery targets by conducting large-scale high-precision protein network analysis” has been partially achieved.Answer (Tohru Natsume)The specific story of new dug discovery target was described taking the example of proteasome assembly factor that was published in Nature.[12][13][14][15]Murata: Cooperation of multiple chaperones required for the assembly of mammalian 20S proteasomes, Molecular Cell, 24(6), 977-984 (2006). H. Iioka, S. Iemura, T. Natsume and N. Kinoshita: Wnt signalling regulates paxillin ubiquitination essential for mesodermal cell motility, Nat. Cell Biol., 9(7), 813-821 (2007). R.H. Lee, H. Iioka, M. Ohashi, S. Iemura, T. Natsume and N. Kinoshita: XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway, Embo J., 26(15), 3592-3606 (2007). M. Komatsu, S. Waguri, M. Koike, Y.S. Sou, T. Ueno, T. Hara, N. Mizushima, J. Iwata, J. Ezaki, S. Murata, J. Hamazaki, Y. Nishito, S. Iemura, T. Natsume, T. Yanagawa, J. Uwayama, E. Warabi, H. Yoshida, T. Ishii, A. Kobayashi, M. Yamamoto, Z. Yue, Y. Uchiyama, E. Kominami and K. Tanaka: Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice, Cell, 131(6), 1149-1163 (2007).T. Natsume: Chemical biology project in Japan, Pharmacia, 42(5), 457-461 (2006) (In Japanese).Received original manuscript January 17, 2008Revisions received February 8, 2008Accepted February 8, 2008AuthorsShun-ichiro IemuraCompleted Masters course (Agricultural Chemistry) at Graduate School of Agricultural Sciences, Kagoshima University in 1991. Doctor of Science (Molecular Biology, National Institute of Basic Biology) in 1999. Joined AIST in 2002. Currently chief researcher at Biomedicinal Information Research Center. In this paper, worked on large-scale analysis of protein interaction using mass spectrometry. Developed refining sample preparation methods for high-throughput mass spectrometry analysis, and was in charge of organizing operation of high throughout analytical platform in clean room.Tohru NatsumeAfter participating in projects of 4 universities, 1 company, and 1 national research institute, or total 9 laboratories, (48)−

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