Systems analysis of molecular networks based on biochemical computational simulations
| Project/Area Number |
15014206
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | University of Tokyo |
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Principal Investigator |
KURODA Shinya University of Tokyo, Graduate School of Information Science and Technology, Project Associate Professor, 大学院情報理工学系研究科, 科学技術振興特任教員 (50273850)
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| Co-Investigator(Kenkyū-buntansha) |
KAWATO Mitsuo Advanced Telecommunications research institute international, Director, 脳情報研究所, 所長(研究職) (10144445)
MAEDA Akio University of Tokyo, Graduate School of Information Science and Technology, Project Research Associate, 大学院情報理工学系研究科, 科学技術振興特任教員 (30361538)
SASAGAWA Satoru University of Tokyo, Graduate School of Information Science and Technology, Project Researcher, 大学院情報理工学系研究科, 科学技術振興特任研究員 (80345115)
OZAKI Yuichi University of Tokyo, Graduate School of Information Science and Technology, Project Researcher, 大学院情報理工学系研究科, 科学技術振興特任研究員 (70345114)
SIVAKUMARAN Sudhir 東京大学, 大学院・情報理工学系研究科, 科学技術振興特任研究員(常勤形態) (70361540)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥32,000,000 (Direct Cost: ¥32,000,000)
Fiscal Year 2004: ¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2003: ¥16,000,000 (Direct Cost: ¥16,000,000)
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| Keywords | signal transduction / systems biology / bioinformatics / 生体生命情報 |
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| Research Abstract |
Many biological phenomena are regulated by their intrinsic biological networks. These networks contain both linear and non-linear relationship, which make difficult to understand the whole networks at the systems level. In this study, to overcome these difficulties we tried to utilize two interdependent approaches, prediction by in silico computational simulation and validation by in vivo experiments. We focused on two phenomena, 1) molecular network in myosin light chain (MLC) phosphorylation and 2) quantitative analysis of cerebellar long-term depression (LTD).
1)Dynamics of throbin-induced MLC phosphorylation in endothelium is composed of initial and sustained phases. By the literature-based simulation model we succeeded in the reproduction of only the initial but not the sustained phase. The model pinpointed us the missing pathway may underlie downstream of Rho-kinase. We experimentally validated the sustained activation of Rho-kinase by the phosphorylation of MYPT1 (myosin phosphatase target subunit 1), a substrate of Rho-kinase, which exhibited hysteresis.
2)We developed a computational model of postsynaptic Ca^<2+> increase in cerebellar LTD. The model revealed that Ca^<2+> increase is induced by a regenerative cycle by Ca^<2+>-induced Ca^<2+> release (CICR) via IP3 receptors, and that the latency of IP3 generation by PF stimulation produces timing window of spike-timing dependent LTD in the cerebellum. Moreover, we developed a unified model of the Ca^<2+> increase and downstream signaling cascades. The unified model raised the possibility that postsynaptic spines of the cerebellum tune their own synaptic strength for adequate Ca^<2+> increase for robust LTD.
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Report
(3 results)
Research Products
(13 results)
