数理モデルを用いたキナーゼと転写の定量的評価

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  • Quantitative evaluation of kinase activities and transcriptional regulation using mathematical model

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<p>Cells respond to external stimuli and eventually make the decision for survival, growth and differentiation. In this process, outcomes of the kinase activities of signal transduction pathways and transcription factors often show dynamically rich, highly quantitative behaviors over time. This quantitative response is, however, eventually converted into a qualitative response and a binary decision (eg. survival or cell death), at the stage of cell decision. A binary decision of a cell is made based on the combined activities of multiple molecules. However, the molecular mechanism of threshold setting of the responses in each cellular context is still unknown. To reveal this mechanism, we analyze the experimental data of signaling and multi-Omics using a mathematical model and extract logical rules in the cell decision mechanism and the target molecules (eg. marker molecules) that define the cellular threshold. </p><p>Our analysis, using NF-kB and ErbB receptor signaling as model systems, indicates that the high-order inter-molecular formation in signaling pathways and epigenetic regulation plays an important role for binary activation of gene expression, and this mechanism might act as a threshold setting for cell regulation. I will introduce our modeling approach for NF-kB signaling pathway, single cell transcriptome and epigenetics.</p>

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