細胞内／細胞間シグナル伝達系の数理モデル
We introduce a new modeling method to describe organ morphogenesis including both machanical and chemical aspects. To illustrate the method, we study the growth of vertebrate limb buds, in which a limb bud protrudes from a flat lateral plate and extends proximally in a self-organized manner. We examine the dependence of the limb bud shape on various mechano-chemical factors and show that specifying the spatio-temporal pattern of active cell proliferation area by morphogen gradient is able to guide organ morphogenesis.
In HSV reproductive process, temporal ordered gene expression pattern appears. The genes of HSV are classified into three groups, immediate early, early and late gene, by the timing of their expressions. The expression pattern is regulated by the genetic cascade. Immediately after the infection, immediate early genes encoding the transcriptional regulator are expressed. Early and late genes are sequentially expressed under the control of immediate early gene products. Early genes encode the enzymes contributing to DNA replication and nucleic acid metabolism. While late genes encode the proteins composing of the envelop of virion. In this study, we investigate the role of temporal ordered gene expression pattern in reproduction of HSV. And we also examine how the expression pattern of HSV develops.
A peculiar property of the cyanobacterial circadian clock is that circadian oscillations of cyanobacterial KaiC phosphorylation can be reconstituted in vitro. In this talk we propose a regulatory mechanism of KaiC phosphorylation for circadian oscillations in cyanobacteria.
The model can explain (1) the sustained oscillation of mRNA and protein abundance when the expression of kaiBCgene is regulated by KaiC protein, and (2) the sustained oscillation of phosphorylated KaiC when transcription and translation processes are inhibited and total protein abundance is fixed. Finally, we discuss the physiological relevance of these.
Understanding of intracellular systems requires characterization of the systems from the viewpoint of dynamics. The characterization of an intracellular system typically relies on the population-level experiments. However, only averaged behaviors of the system in a population of cells are observed in the population-level experiments. Because of a variety of non-genetic variability, the averaged behaviors of an intracellular system can drastically differ from its single-cell-level behaviors.
In this talk, I will show some results of theoretical and experimental analysis that demonstrate the importance of the characterization with the single-cell-level experiments.
ERK signaling network has been shown to elicit distinct functions via distinct temporal activation patterns. In PC12 cells, transient and sustained activation of ERK lead to proliferation and differentiation, respectively. However, how the ERK signalling network converts extracellular information into distinct temporal activation patterns of a certain molecule remains unknown. To address this issue, we developed a kinetic computer simulation model of EGF- and NGF-dependent ERK signalling networks by constraining the in silico dynamics of the networks based on the in vivo dynamics measurement in PC12 cells. This in silico model could consistently reproduce measured in vivo dynamics in dose- and temporal-dependent manners in growth factors. Theoretical analysis of the in silico model enables us to extract essential and simple frameworks of the characteristics of the complex ERK signalling networks. Using this in vivo validated model, we predicted in silico and validated in vivo that the Ras and Rap1 systems specifically capture the temporal rate and concentration of growth factors, and encode these distinct physical properties of growth factors into transient and sustained ERK activation, respectively.
Biochemical reactions occurring in the cell are typically represented by complex networks with huge number nodes denoting bio-molecules and links representing biochemical reactions between bio-molecules. The strategy of attacking the whole bio-complex networks for systems analysis is to 'divide-and-conquer'. That is, the whole networks are decomposed into smaller modules with elements tightly connected among themselves. One of most common features of cell cycle regulation networks is that they are interconnected by multiple feedback connections. So, at first, we will present the dynamics of isolated negative and positive feedback loops, which will be the building blocks of the whole cell cycle regulation network. Then we will present dynamics of the interlocked or cascaded networks of positive and negative feedback loops. And the design principle of the cascaded networks will be also discussed. By the strategy of 'divide and conquer, and then synthesize', we could explain the certain dynamic features of cell cycle regulation in the budding yeast and fission yeast.