2014 Fiscal Year Final Research Report
Mathematical model for cellular dysfunctions caused by failure in post-translational signal transduction
| Project Area | Regulation of signal transduction by post-translational modifications and its pathogenic dysregulation |
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| Project/Area Number |
22117008
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2010-04-01 – 2015-03-31
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| Keywords | NF-kappaB / stress granule / cancer / computer simulation / spatio-temporal dynamics |
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| Outline of Final Research Achievements |
Dysfunction in intracellular signal transduction is a cause of many diseases. Majority of computational signal transduction research has been focused on pathways. Since a cell is 3D entity, we tested the effect of spatial parameters on the signal transduction.
First we found that oscillation of transcription factor NF-kB was regulated by diffusion coefficient, nuclear transport, and nuclear/cytoplasmic volume ratio, and in addition, while diffusion coefficient and export for mRNA from the nucleus regulated persistency of NF-kB oscillation, IkB import to the nucleus exclusively regulated oscillation frequency. Second, we found that the fusion of stress granules (SGs) was important for their dynamics, and simulation predicted gamma distribution of SG size, which was confirmed by experiments.
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| Free Research Field |
シグナル伝達、シミュレーション
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