統合的多階層生体機能学領域の確立とその応用

2010 Fiscal Year Annual Research Report

• Project Area: Establishment of Integrative Multi-level Systems Biology and its Applications
• Project/Area Number: 22136001
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Research Institution: Osaka University
• Principal Investigator: 倉智 嘉久 大阪大学, 医学系研究科, 教授 (30142011)
• Co-Investigator(Kenkyū-buntansha): 北野 宏明 沖縄科学技術研究基盤整備機構, オープンバイオロジーユニット, 研究員 (80500256) ; 井上 隆司 福岡大学, 医学部, 教授 (30232573) ; 鈴木 洋史 東京大学, 医学部附属病院, 教授 (80206523) ; 大槻 純男 東北大学, 薬学研究科, 准教授 (60323036)
• Keywords: システム生物学 / 生理学 / 生物物理 / 心臓 / 不整脈 / 薬物動態 / 全身循環 / 代謝

Research Abstract

初年度である本年度は研究体勢の確立を目指した。研究開始後直ちに総括班会議をおこない、領域計画の再確認と共同研究体制を具体化した。さらに本領域の参画研究者が一同に会する領域全体会議(第一回)を開いた。この会議では、本新学術領域研究の方向性を明確にし、5年間の到達目標と研究方法、計画班の役割の確認をおこなった。
さらに公開シンポジウムを開催した。このシンポジウムでは新たにスタートする本研究プロジェクトの計画概要や具体的到達目標、期待される波及効果等を広く説明し、関連分野研究者に領域の情報を提供して便宜を図るとともに、統合的生命科学の現状や課題、医療や産業の分野で何が求められているのか議論を深めることができた。
年度の後半には、研究項目毎の研究会議を開催し具体的研究課題に関して意見交換をおこなった。いくつかの領域内共同研究がスタートしている。年度末には再度、領域全体会議(第二回)を開催し、研究状況の把握や問題意識の共有、次年度以降の領域推進に関するロードマップの決定をおこなった。さらに公募研究班を迎え入れる準備をおこなった。
また、本領域の発足や、参画研究者情報、各研究分野から上がった成果、及びそれを統合した理論を速やかに提供できる環境の構築をおこなった。具体的には、領域のホームページをウェブ上に公開し、またニュースレターの作成を始めた。このような方法により、領域内の研究成果に領域外の研究者や一般市民がアクセスできる状態を構築し、評価や批判的議論を得られるように、そして関心を持つ研究者の利便性を図る取組みをおこなった。

Research Products

• [Journal Article] Dual signaling pathways of arterial constriction by extracellular UTP in the rat (2011)
  • Author(s): Megumi Sugihara, Hiromitsu Morita, Miho Matsuda, Hisanori Umebayashi, Shunichi Kajioka, Shinichi Ito, Motohiro Nishida, Ryosuke Inoue, Toshiko Futatsuki, Jun Yamazaki, Yasuo Mori, Ryuji Inoue, Yushi Ito, Kihachiro Abe, Masato Hirata
  • Journal Title: Journal of Pharmacological Sciences Volume: 115(3) Pages: 293-308
  • DOI: 10.1254/jphs.10281FP
  • Peer Reviewed
• [Journal Article] Roles of Subcellular Na^+ Channel Distributions in the Mechanism of Cardiac Conduction (2011)
  • Author(s): Kunichika Tsumoto, Takashi Ashihara, Ryo Haraguchi, Kazuo Nakazawa, Yoshihisa Kurachi
  • Journal Title: Biophysical Journal Volume: 100(3) Pages: 554-563
  • Peer Reviewed
• [Journal Article] Transmural dispersion of repolarization determines scroll wave behavior during ventricular tachyarrhythmias (2011)
  • Author(s): Ryo Haraguchi, Takashi Ashihara, Tsunetoyo Namba, Kunichika Tsumoto, Murakami Shingo, Yoshihisa Kurachi, Takanori Ikeda, Kazuo Nakazawa
  • Journal Title: Circulation Journal Volume: 75(1) Pages: 80-88
  • Peer Reviewed
• [Journal Article] Regulation of cardiovascular TRP channel functions along the NO-cGMP-PKG axis (2011)
  • Author(s): Ryuii Inoue, Juan Shi, Zhong Jian, Yuko Imai
  • Journal Title: Expert Review of Clinical Pharmacology Volume: 3(3) Pages: 347-360
  • Peer Reviewed
• [Journal Article] NPC2 regulates biliary cholesterol secretion via stimulation of ABCGS/G8-mediated cholesterol transport (2011)
  • Author(s): Yoshihide Yamanashi, Tappei Takada, Takashi Yoshikado, Jun-ichi Shoda, Hiroshi Suzuki
  • Journal Title: Gastroenterology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Serum Metabolomics Reveals γ-Glutamyl Dipeptides as Biomarkers for Discrimination among Different Forms of Liver Disease (2011)
  • Author(s): Tomoyoshi Soga, Masahiro Sugimoto, Masashi Honma, Masayo Mori, Kaori Igarashi, Kasumi Kashikura, Satsuki Ikeda, Akiyoshi Hirayama, Takehito Yamamoto, Haruhiko Yoshida, Motoyuki Otsuka, Shoji Tsuji, Yutaka Yatomi, Tadayuki Sakuragawa, Hisayoshi Watanabe, Kouei Nihei, Takafumi Saito, Sumio Kawata, Hiroshi Suzuki, Masaru Tomita, Makoto Suematsu
  • Journal Title: Journal of Hepatology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Rab27a and Rab27b are involved in stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells (2011)
  • Author(s): Yoshiaki Kariya, Masashi Honma, Akiko Hanamura, Shigeki Aoki, Tadashi Ninomiya, Yuko Nakamichi, Nobuyuki Udagawa, Hiroshi Suzuki
  • Journal Title: Journal of Bone and Mineral Research Volume: (In press)
  • Peer Reviewed
• [Journal Article] Simultaneous absolute quantification of 11 cytochrome P450 isoforms in human liver microsomes by liquid chromatography tandem mass spectrometry with in silico target peptide selection (2011)
  • Author(s): Hirotaka Kawakami, Sumio Ohtsuki, Junichi Kamiie, Takashi Suzuki, Takaaki Abe, Tetsuya Terasaki
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 100 Pages: 341-352
  • Peer Reviewed
• [Journal Article] A structural determinant for the control of PIP_2 sensitivity in G protein-gated inward rectifier K^+ channels (2010)
  • Author(s): Atsushi Inanobe, Atsushi Nakagawa, Takanori Matsuura, Yoshihisa Kurachi
  • Journal Title: Journal of Biological Chemistry Volume: 285(49) Pages: 38517-38523
  • Peer Reviewed
• [Journal Article] Large-scale analysis of network bistability for human cancers (2010)
  • Author(s): Tetsuya Shiraishi, Shinako Matsuyama, Hiroaki Kitano
  • Journal Title: PLoS Computational Biology Volume: 16(7) Pages: e1000851
  • Peer Reviewed
• [Journal Article] A comprehensive molecular interaction map of the budding yeast cell cycle. (2010)
  • Author(s): Kazunari Kaizu, Samik Ghosh, Yukiko Matsuoka, Hisao Moriya, Yuki Shimizu-Yoshida, Hiroaki Kitano
  • Journal Title: Molecular Systems Biology Volume: 6 Pages: 415
  • Peer Reviewed
• [Journal Article] A comprehensive map of the mTOR signaling network (2010)
  • Author(s): Etienne Caron, Samik Ghosh, Yukiko Matsuoka, Dariel Ashton-Beaucagel, Marc Therrien, Sebastien Lemieux, Claude Perreault, Philippe P Roux, Hiroaki Kitano
  • Journal Title: Molecular Systems Biology Volume: 6 Pages: 453
  • Peer Reviewed
• [Journal Article] システムバイオロジーにおける情報基盤 (2010)
  • Author(s): 北野宏明、松岡由希子、Samik Ghosh
  • Journal Title: 計測と制御 Volume: 49(8) Pages: 507-512
  • Peer Reviewed
• [Journal Article] 細胞シミュレータCellDesignerの設計と実装 (2010)
  • Author(s): 舟橋啓、松岡由希子、上樂明也、瀧沢大夢、広井賀子、Samik Ghosh、菊池紀広、北野宏明
  • Journal Title: 計測と制御 Volume: 49(8) Pages: 531-536
  • Peer Reviewed
• [Journal Article] Connecting the dots : role of standardization and technology sharing in biological simulation (2010)
  • Author(s): Samik Ghosh, Yukiko Matsuoka, Hiroaki Kitano
  • Journal Title: Drug Discovery Today Volume: 15 Pages: 1024-1031
  • Peer Reviewed
• [Journal Article] Inhibition of TRPC6 Channel Activity contributes to the Anti-hypertrophic Effects of Natriuretic Peptides-guanylyl cyclase-A signaling in the heart (2010)
  • Author(s): Hideyuki Kinoshita, Koichiro Kuwahara, Motohiro Nishida, Jian Zhong, Xianglu Rong, Shigeki Kiyonaka, Yoshihiro Kuwabara, Hitoshi Kurose, Ryuji Inoue, Yasuo Mori, Yuhao Li, Yasuaki Nakagawa, Masao Murakami, Masaki Harada, Shinji Yasuno, Satoru Usami, Masataka Fujiwara, Yuko Yamada, Takeya Minami, Kenji Ueshima, Eric N.Olson, Kazuwa Nakao
  • Journal Title: Circulation Research Volume: 106(12) Pages: 1849-1860
  • Peer Reviewed
• [Journal Article] Phosphorylation of TRPC6 channels at Thr^<69> is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition (2010)
  • Author(s): Motohiro Nishida, Kenta Watanabe, Yoji Sato, Michio Nakaya, Naoyuki Kitajima, Tomomi Ide, Ryuji Inoue, Hitoshi Kurose
  • Journal Title: Journal of Biological Chemistry Volume: 285(17) Pages: 13244-13253
  • Peer Reviewed
• [Journal Article] Ca^<2+> Influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells (2010)
  • Author(s): Takuro Numaga, Motohiro Nishida, Shigeki Kiyonaka, Kenta Kato, Masahiro Katano, Emiko Mori, Tomohiro Kurosaki, Ryuii Inoue, Masaki Hikida, James W Putney, Jr, Yasuo Mori
  • Journal Title: Journal of Cell Science Volume: 123(6) Pages: 927-938
  • Peer Reviewed
• [Journal Article] Itraconazole-induced cholestasis : involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4 (2010)
  • Author(s): Takashi Yoshikado, Tappei Takada, Takehito Yamamoto, Hiroko Yamaji, Kousei Ito, Tomofumi Santa, Hiromitsu Yokota, Yutaka Yatomi, Haruhiko Yoshida, Jun Goto, Shoji Tsuji, Hiroshi Suzuki
  • Journal Title: Molecular Pharmacology Volume: 79(2) Pages: 241-250
  • Peer Reviewed
• [Presentation] 膜脂質メッセンジャーを介した受容体・機械刺激Ca^<2+>応答の統合制御機構 (2011)
  • Author(s): 井上隆司、今井裕子、斎郷平、市川純、森誠之
  • Organizer: 第88回日本生理学会大会シンポジウム「脂質メディエーターの細胞機能と疾患」
  • Place of Presentation: パシフィコ横浜、横浜(招待講演)
  • Year and Date: 2011-03-29
• [Presentation] 定量的標的プロテオミクスによるファーマコプロテオミクスアプローチ (2011)
  • Author(s): 大槻純男
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡、静岡(招待講演)
  • Year and Date: 2011-03-29
• [Presentation] Systems Drug Discovery and Platform Design. (2011)
  • Author(s): Hiroaki Kitano
  • Organizer: 15^<th> Human Genome Meeting : Genomics of Human Diversity and Heritable Disorders
  • Place of Presentation: Dubai International Convention & Exhibition Centre, Dubai, UAE(招待講演)
  • Year and Date: 2011-03-17
• [Presentation] Systems Medicine and Systems Drug Design as the Grand Challenge in 21st Century (2011)
  • Author(s): Hiroaki Kitano
  • Organizer: BioComplexity Symposium : Systems Biology Approach to Systems Drug Discovery and Systems Medicine
  • Place of Presentation: NUHS Tower Block, Singapore(招待講演)
  • Year and Date: 2011-02-14
• [Presentation] システムバイオロジーと創薬・医療応用 (2011)
  • Author(s): 北野宏明
  • Organizer: 「生命をはかる」研究会 第33回研究会
  • Place of Presentation: 東陽テクニカ(東京都)(招待講演)
  • Year and Date: 2011-02-07
• [Presentation] Systems Drug Design (2010)
  • Author(s): Hiroaki Kitano
  • Organizer: Systems Biology at the Interface of Metabolism and Signal Transduction
  • Place of Presentation: VU University Amsterdam, The Netherlands(招待講演)
  • Year and Date: 2010-12-17
• [Presentation] Quantitative semi-simultaneous imaging of Ca^<2+> and Ca^<2+>-dependent calmodulin interactions by FRET (2010)
  • Author(s): Masayuki Mori, Yuko Imai, Kyohei Isuki, Ryuji Inoue
  • Organizer: The 9^<th> Korea--Japan Joint Symposium of Brain Sciences, and Cardiac and Smooth Muscles
  • Place of Presentation: Keitenkaku, Kagoshima(招待講演)
  • Year and Date: 2010-11-26
• [Presentation] システム創薬-がんのシステム的理解と創薬への応用- (2010)
  • Author(s): 北野宏明
  • Organizer: 神奈川科学技術アカデミー(KAST)教育講座 システムバイオロジー講座
  • Place of Presentation: 神奈川科学技術アカデミー(KAST),神奈川(招待講演)
  • Year and Date: 2010-11-18
• [Presentation] PISCS (pharmacokinetic interaction significance classification system) : toward seamless drug-interaction alert (2010)
  • Author(s): Akihiro Hisaka
  • Organizer: Pharmaceutical sciences world congress (PSWC 2010)
  • Place of Presentation: Morial Convention Center, New Orleans, USA.
  • Year and Date: 2010-11-15
• [Presentation] Systems Robustness and Systems Failures in Biology, Medicine, and Engineering (2010)
  • Author(s): Hiroaki Kitano
  • Organizer: A^*STAR Scientific Conference 2010
  • Place of Presentation: A^*STAR, Singapore(招待講演)
  • Year and Date: 2010-11-10
• [Presentation] Systems Biology and Drug Discovery (2010)
  • Author(s): Hiroaki Kitano
  • Organizer: National University of Singapore, Biochemistry Seminar
  • Place of Presentation: National University of Singapore, Singapore(招待講演)
  • Year and Date: 2010-11-08
• [Presentation] 定量的標的プロテオミクスによって拓かれる新しい創薬研究への展開 (2010)
  • Author(s): 大槻純男
  • Organizer: 創剤フォーラム第16回シンポジウム
  • Place of Presentation: アルカディア市ヶ谷、東京(招待講演)
  • Year and Date: 2010-10-22
• [Presentation] An Open-flow Paradigm for Curation and Enrichment of Biological Pathways. (2010)
  • Author(s): Samik Ghosh, Yukiko Matsuoka, Hiroaki Kitano
  • Organizer: International Conference on Systems Biology (ICSB) 2010
  • Place of Presentation: Edinburgh International Conference Centre, UK
  • Year and Date: 2010-10-12
• [Presentation] PathText : Integrating Text Mining Resources with Biological Pathway Visualizations. (2010)
  • Author(s): Brian Kemper, Takuya Matsuzaki, Yukiko Matsuoka, Yoshimasa Tsuruoka, Hiroaki Kitano, Jun'ichi Tsujii, Sophia Ananiadou
  • Organizer: International Conference on Systems Biology (ICSB) 2010
  • Place of Presentation: Edinburgh International Conference Centre, UK
  • Year and Date: 2010-10-12
• [Presentation] Posttraslational regulation of Abcc2 through sumoylation (2010)
  • Author(s): Hiroshi Suzuki, Shuichi Sekine, Toshiharu Horie, Kousei Ito
  • Organizer: Falk Symposium 175 : XXI International Bile Acid Meeting
  • Place of Presentation: Freiburg, Germany
  • Year and Date: 2010-10-07
• [Presentation] Systems drug discovery and software platform for healthcare research and services. (2010)
  • Author(s): Hiroaki Kitano
  • Organizer: International Conference on Bioinformatics (InCoB)
  • Place of Presentation: Waseda University, Tokyo(招待講演)
  • Year and Date: 2010-09-27
• [Presentation] 多階層統合生体シミュレーションから生命機能の理解と予測医学の実現を目指して (2010)
  • Author(s): 北野宏明、井上隆司、鈴木洋史、倉智嘉久
  • Organizer: 新学術領域研究「多階層生体機能学」キックオフシンポジウム
  • Place of Presentation: 大阪大学中之島センター佐治敬三ホール、大阪(招待講演)
  • Year and Date: 2010-09-25
• [Presentation] 次世代のファーマコプロテオミクスと中枢神経作用薬の開発 (2010)
  • Author(s): 大槻純男
  • Organizer: 第20回日本臨床精神神経薬理学会・第40回日本神経精神薬理学会年会合同年会
  • Place of Presentation: 仙台国際センター、仙台(招待講演)
  • Year and Date: 2010-09-17
• [Presentation] Multiplexed-MRM法による膜タンパク質群の一斉定量とファーマコプロテオミクスへの応用 (2010)
  • Author(s): 大槻純男
  • Organizer: 日本分析化学会第59年会
  • Place of Presentation: 東北大学川内キャンパス、仙台(招待講演)
  • Year and Date: 2010-09-16
• [Presentation] Nappによるモデリングとシミュレーションの紹介 (2010)
  • Author(s): 樋坂章博
  • Organizer: 第3回日本ファーマコメトリクス研究会
  • Place of Presentation: 昭和大学、東京
  • Year and Date: 2010-09-03
• [Presentation] タンパク質の定量によって拓かれる新しい創薬研究 (2010)
  • Author(s): 大槻純男
  • Organizer: 第23回バイオメディカル分析科学シンポジウム
  • Place of Presentation: ホテル大観荘、松島(招待講演)
  • Year and Date: 2010-07-23
• [Presentation] Hitting Robustness (2010)
  • Author(s): Hiroaki Kitano
  • Organizer: 16^<th> World Congress on Basic and Clinical Pharmacology (WorldPharma 2010)
  • Place of Presentation: Bella Center, Copenhagen, Denmark(招待講演)
  • Year and Date: 2010-07-19
• [Presentation] 心血管CaチャネルTRPC6の機能と制御-受容体機械刺激応答性のリン酸化を介した統合的制御機構- (2010)
  • Author(s): 井上隆司
  • Organizer: 第13回札幌高血圧セミナー
  • Place of Presentation: ホテルニューオータニ札幌、札幌(招待講演)
  • Year and Date: 2010-07-09
• [Presentation] Rationale of Garuda and introduction to Garuda-2 workshop (2010)
  • Author(s): Hiroaki Kitano
  • Organizer: Garuda Two Workshop
  • Place of Presentation: Manchester Interdisciplinary Biocentre, UK(招待講演)
  • Year and Date: 2010-07-05
• [Remarks]
  • URL: http://hd-physiology.jp/
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/pharma2/singaku/
• [Patent(Industrial Property Rights)] ネットワークモデル統合装置、ネットワークモデル統合システム、ネットワークモデル統合方法、および、プログラム (2010)
  • Inventor(s): 北野宏明、松岡由希子、サミックゴーシュ
  • Industrial Property Rights Holder: 独立行政法人沖縄科学技術研究基盤整備機構、特定非営利活動法人システム・バイオロジー研究機構
  • Industrial Property Number: 特願2010-224308
  • Filing Date: 2010-10-01