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>Invited Speaker / 招待講演

	【December, 3】	13:30-14:15	Prof. Kwok Wing Stephen Tsui	Abstract	Profile
		14:55-15:40	Prof. Shinichi Morishita	Abstract	Profile
	【December, 4】	11:10-12:00	Prof. Kousaku Okubo	Abstract	Profile
		14:00-14:50	Prof. Sunghoon Kim	Abstract	Profile
		15:50-16:40	Prof. Motonori Ota	Abstract	Profile

Prof. Kwok Wing Stephen Tsui Professor School of Biomedical Sciences, The Chinese University of Hong Kong Abstract Next Generation DNA Sequencing and Bioinformatics: Bottlenecks and Opportunities With the emergence of high-throughput genome sequencers from various companies including Applied Biosystems, Illumina and Roche, the conventional approach of genomic investigation has been revolutionized and new applications involving these sequencers have been designed and adopted not only in genome centres, but also in general laboratories working on biological and biomedical research. These genome sequencers are capable of generating terabytes of raw data daily, posing a big challenge to various aspects of bioinformatics and computational biology, e.g. data quality assurance, data storage, cross platform data analysis standards, data comparison, data annotation and gene network analysis. The problem will become more prominent when this technology is applicable in areas such as clinical diagnosis and personalized medicine. In foreseeable future, we believe bioinformatics will be one of the major bottlenecks of the further development of biological sciences. In this talk, some of the genome projects in the Centre for Microbial Genomics and Proteomics of the Chinese University of Hong Kong will be used as examples to unravel the difficulties researchers generally come across in the area of bioinformatics. Next, based on our understanding of the recent development in computational biology, possible solutions to these difficulties will be discussed. Finally, the future opportunities in bioinformatics and next generation DNA sequencing technology will be presented. We believe this talk can provide useful insights and future research directions for audiences who are interested in bioinformatics and computation biology. References (1) Sung JJY, et al. "Genotype-specific genomic markers associated with primary hrpatomas, based on complete genomic sequencing of hepatitis B virus."Journal of Virology, 2008;82(7):3604-11. (2) Chim SSC, et al. "Genomic characterisation of the senere acute respiratory syndrome coronavirus of Amoy Gardens outbreak in Hong Kong" The Lancet, 2003;362(9398):1807-8. (3) Tsui SKW, et al. "Coronavirus genomic-sequence variations and the epidemiology of the severe acute respiratory syndrome" The New England Journalof Medicine, 2003;349(2):187-8. (4) Hwang DM, et al. "A genome-based resource for molecular cardiovascular medicine: toward a compendium of cardiovascular genes."Circulation Journal, 1997;96(12):4146-203. (5) Liew CC, et al. "A catalogue of genes in the cardiovascular system as identified by expressed sequence tags" Prpceedings of the National Academy of Sciences of the United States of America, 1995;91(22):10645-9. 　 　 Profile Education 1992-1995 Doctor of Philosophy in Biochemistry, The Chinese University of Hong Kong 1985-1986 Diploma of Education, The Chinese University of Hong Kong 1981-1985 Bachelor of Science (Hons.) in Chemistry, The Chinese University of Hong Kong 1975-1981 Ho Lap College

Prof. Shinichi Morishita Professor Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo Abstract Encouraging Bioinformatics Researchers to Design Biological Research in the Era of Genome Information Big Bang Sequencing genomes itself was a serious research problem when sequencing was extremely costly, laborious and time-consuming several years ago. To date, the wide spread of next-generation sequencers has been making it possible to collect enormous volume of genome-wide sequence data with less effort in a fairly short period. Because sequencing is not a limiting factor today, we are able to study a variety of long-standing biological questions, such as effects of genetic variations by re-sequencing the genomes of human and other species, unknown genomes by de-novo sequencing, and genome-wide epi-genomic states including chromatin structure and DNA methylation. The bottleneck today would be sample selection/collection and data analysis, which are likely to take much longer time than sequencing. It is crucial for us to be very careful in designing feasible research plans that address fundamental biological questions and present a fantastic roadmap to the solution, considering limitations of next-generation sequencing and capacity of computational resources. In this planning process, bioinformatics researchers are expected to lead the discussion more enthusiastically through the collaboration with biologists and medical scientists. In this talk, I will introduce good and bad experiences that may be helpful for others. 　　 References (1) Sasaki S, et al. "Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites." Science, 2009 Jan 16;323(5912):401-4. (2) Qu W, et al. "Efficient frequency-based de novo short-read clustering for error trimming in next-generation sequencing." Genome Research, 2009 Jul;19(7):1309-15. (3) Saito TL, et al. "UTGB toolkit for personalized genome browsers." Bioinformatics, 2009 Aug 1;25(15):1856-61. (4) Ahsan B, et al. "MachiBase: a Drosophila melanogaster 5'-end mRNA transcription database." Nucleic Acids Research, 2009 Jan;37(Database issue):D49-53. (5) International Silkworm Genome Consortium. "The genome of a lepidopteran model insect, the silkworm Bombyx mori." Insect Biochemistry and Molecular Biology, 2008 Dec;38(12):1036-45. (6) Nakatani Y, et al. "Reconstruction of the vertebrate ancestral genome reveals dynamic genome reorganization in early vertebrates." Genome Research, 2007 Sep;17(9):1254-65. (7) Kasahara M, et al. "The medaka draft genome and insights into vertebrate genome evolution." Nature, 2007 Jun 7;447(7145):714-9. 　 　 Profile 　 Employment 2003-present Professor, Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo 1999-2003 Associate Professor, Department of Complexity Science and Engineering, Graduate School of Frontier Sciences, University of Tokyo Adjunct Associate Professor, Department of Information Science, Faculty of Science, University of Tokyo 1997-2000 Visiting Associate Professor, Institute of Medical Science 1990-1992 Visiting Researcher, Department of Computer Science, Stanford University IBM Almaden Research Center 1985-1997 Researcher, IBM Japan Education 1990 Ph.D., Department of Information Science, Graduate School of Science, University of Tokyo, Japan 1985 M.S., Department of Information Science, Graduate School of Science, University of Tokyo, Japan 1983 B.S., Department of Information Science, Faculty of Science, University of Tokyo, Japan

Prof. Kousaku Okubo Professor National Institute of Genetics, Research Organization of Information and Systems, Japan Abstract デジタル科学における独占と共有の賢いバランス 科学の実践法はデジタル革命によって急速に変化しています。 (1)天文学のデジタルイメージング機器　(2)生命科学のマイクロアレイやシーケンサー (3)地球科学のワイアレスセンシング　(4)気象学のシミュレーション計算機　などのデジタル科学はマッシブデータセットを生成します。　データはアナログ時代のような「準備された質問への答え」ではなく、多くの科学者の観察を代行し、実験計画を助け、自由な理論形成やモデル化の材料として幾通りにも利用でき、枯渇しない科学の燃料です。　科学のプロセス―観察、実験、理論、モデル化―の全てのステップがこのデータを駆使する手法に変わりつつあります。 生命科学では1990年代初め米バイオベンチャーによる機能不明のDNA配列の特許出願で「燃料としての基盤データ」が社会に知られ、機能不明配列の使用権を売る米データビジネスが耳目を集めました（参考１）。　わが国では主に政府科学プロジェクト（注１）が基盤データの生産を担いその成果は次々とデータベースとして「公開」されてきました。　しかしその成果が統合的に「利用できない」という問題が指摘されています（注２）。　閲覧できるが利用制限の多い「公開データベース」は写真の転用やパースの禁止されている電子出版科学雑誌（参考２、３）と同じだというわけです。　すべてはデジタル技術が増大させた可能性を古い制度が縛っているのです。 制度の修正がなければ活躍できなくなったデジタル科学に身をおくものとして、調査研究を進めた　デジタル時代にマッチした理想の制度についてわが国と米国の科学制度（参考４-6）、著作権制度(参考7)などを比較して世界の動向（参考８、９）とともに紹介し、わが国のデジタル科学を自由な発想があふれる創造性豊かな科学にする方策について皆様と考えたいと思います。 References （参考1） 坂井昭夫　米国バイオ関連特許の発展とその含意」『経済論叢』第173巻第1号、(2004) （注1） 例として：http://togodb.dbcls.jp/lsdb_project （注2） 例として：http://lifesciencedb.jp/sciencepolicy/(2009) （参考2） 土屋俊ら、オープンアクセス解説、http://www.openaccessjapan.com/about.html(2005) （参考3） ポストゲノム時代に高まるバイオ自然言語処理への期待、情報処理学会誌, Vol.46 No.2(2005） （参考4） http://grants.nih.gov/grants/sharing.htm およびhttp://133.11.132.80/intelligence/report/law/index7.html （参考5） Bits of Power: Issues in Global Access to Scientific Data, National Research Council.(1997) （参考6） A Question of Balance: Private Rights and the Public Interest in Scientific and Technical Databases (1999)およびhttp://www.nap.edu/catalog/11896.html （参考7） �@The Paperwork Reduction Act (44 USC 35) �AThe Office of Management and Budget (OMB) Circular A-130 �B米連邦最高裁判決 499 U.S. 340 (1991) �CCopyright law (17 USC 105) �DThe Freedom of Information Act (FOIA; 5 USC 552) （参考8） http://www.sherpa.ac.uk/juliet/index.php （参考9） OECD 2004 共同声明（邦訳 http://133.11.132.80/intelligence/finality/pdf/finality_01.pdf) および Arberger, et. al., Science, 303, 1777-1778 (2004) 　 　 Profile 　 Employment 1991-1994 Research associate, Institute for Molecular and Cellular Biology, Osaka University 1994-2001 Associate professor, Institute for Molecular and Cellular Biology, Osaka University 2001-2002 Team leader, Expression Profiles Team, Biological Information Research Center, AIST 2002-2004 Professor, Medical Institute of Bioregulation, Kyushu University 2004-current Professor, Laboratory for Gene-Expression Analysis, National Institute of Genetics 2008-current Professor, The Database Center for Life Science (DBCLS) 2009-current President, Center for Information Biology and DNA Data Bank of Japan(CIB-DDBJ) Education 1982 Bachelor (engineering), University of Tokyo 1986 M. B., Osaka University 1991 M. D., Osaka University

Prof. Sunghoon Kim Director The Center for Medicinal Protein Network and Systems Biology, Korea Abstract Roles and Implications of Multi-functional Proteins in Functional Diversification and Networks of Human Genome Completion of human genome project unveiled that we have significantly lower number of genes than we expected. The conflict of gene numbers and organismal complexity is called "N paradox" and throws a challenge for how the limited genes are functionally diversified. In this regard, polypeptides with multiple functions provide one way to overcome the shortage of gene number. These multi-functional or moonlighting proteins are often positioned as molecular hub in protein-protein interaction network and play a critical role in the operation and regulation of biological systems. Another level of functional diversification can be achieved through alternative splicing. Here a novel protein network consisting of human twenty aminoacyl-tRNA synthetases and diverse cellular factors will be introduced as an example of how human genome can be functionally explored through diverse protein-protein interactions and alternative splicing. Considering that the cases of protein multi-functionality and alternative splicing will be more prevalent, understanding the regulation and functional implications of these proteins in the context of biological network is expected to constitute a major subject in post-genome research. References (1) Park SG, et al. "Aminoacyl tRNA synthetases and their connections to disease." Proceedings of the National Academy of Sciences of the United States of America,2008;105(32):11043-9. (2) Park SG, et al. "Hormonal activity of AIMP1/p43 for glucose homeostasis." Proceedings of the National Academy of Sciences of the United States of America,2006;103(40):14913-8. (3) Park SG, et al. "Functional expansion of aminoacyl-tRNA synthetases and their interacting factors: New perspectives on housekeepers." Trends in Biochemical Sciences, 2005;30(10):569-74. (4) Park BJ, et al. "The Haploinsufficient Tumor Suppressor p18 Upregulates p53 via Interactions with ATM/ATR." Cell, 2005;120(2):209-21. (5) Kise Y, et al. "A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase." Nature Structural & Molecular Biology, 2004;11(2):149-156. (6) Sampath P, et al. "Non-canonical Translational Silencing Activity of Glutamyl-prolyl-tRNA Synthetase Sampath." Cell,2004;119(2):195-208. (7) Kim MJ, et al. "Downregulation of fuse-binding protein and c-myc by tRNA synthetase cofactor,p38/JTV-1, for lung differentiation." Nature Genetics, 2003;34(3):330-6. 　 　 Profile 　 Employment 2001-present Professor in Seoul National University 1994-2001 Associate Professor in Sung Kyun Kwan University 1993-1994 Senior Scientist in Cubist Pharmaceuticals, USA 1991-1994 Post-doc. in Massachusetts Institute of Technology, USA 1983-1983 Researcher in Genetic Eng. Center, Korea Advanced Institute of Science and Technology Education 1991 Ph.D., Molecular Biology, Brown University, USA 1983 M.S., Biological Sciences, Korea Advanced Institute of Science and Technology 1981 B.S., Pharmacy, Seoul National University

Prof. Motonori Ota Professor Department of Bioscience and Biotechnology, Nagoya University Abstract 酵素タンパク質の運動、機能、ドメイン構成 タンパク質は生命体の主成分である。細胞の骨格となり、物質を輸送、代謝、合成することで、生命機能維持を担っている。その中でも化学反応の優れた触媒として働く酵素はタンパク質の典型例と目されており、これまでに多くの研究がなされてきた。機能が解明された酵素にはECナンバーが付与されており、これを目印とすることで大規模なデータベース解析が可能である。 酵素に限らずタンパク質は、折りたたまれて立体構造を取り、その形を基盤として機能を発現する。機能発現の際には形そのものが一義的には重要であるが、形がどのように動くか、つまり、構造変化も重要である。 このような背景をふまえ、酵素タンパク質について構造変化と機能の相関、機能とドメイン構成や会合状態との関係、機能を変換させる要因、などを調べた。 タンパク質の立体構造データベースの中には、リガンドをふくんだ状態とふくまない状態の両方で、立体構造が決定されている酵素がある。それらを抜き出して構造変化の度合いを調べた。その結果、加水分解酵素はほとんど構造変化をせずリガンド結合し、それを水に晒しながら反応を触媒するのに対し、転移酵素は大きく構造変化をすることでリガンドを抱え込み、水から遮蔽して反応を触媒することがわかった。 酵素の触媒ドメインに着目すると、相同なドメインが加水分解酵素にも転移酵素にも見られることがある。このような事例を収集し、リガンドの水への露出を調整する機構を調べた。その結果、相同な転移酵素と加水分解酵素ではドメイン構成か会合状態が異なっている場合が多く、転移酵素ではリクルートされたドメインがリガンドのカバーとなることで、水からの遮蔽を実現していることがわかった。 References (1) Koike R, et al. "Protein structural change upon ligand binding correlates with enzymatic reaction mechanism." Journal of Molecular Biology, 2008;379(3):397-401. (2) Koike R, et al. "Alteration of oligomeric state and domain architecture is essential for functional transformation between transferase and hydrolase with the same scaffold." Protein Science, 2009;18(10):2060-6. 　 　 Profile 　 Employment 2008-present Professor, Nagoya University 2002 Associate Professor, Tokyo Institute of Technology 1996 Assistant Professor, National Institute of Genetics 1996 JSPS Research Fellow 1994 Researcher, Protein Engineering Research Institute 1990 Researcher, Tonen Corporation Education 1996 Ph. D. Waseda University (Applied Physics, Aizawa Laboratory) 1990 M. S. Waseda University (Applied Physics, Aizawa Laboratory)

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