2017 Fiscal Year Annual Research Report
Non-equilibrium phase transitions in multicellular system
Project/Area Number |
17J07573
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Research Institution | The University of Tokyo |
Principal Investigator |
楼 玉テイ 東京大学, 新領域創成科学研究科, 特別研究員(DC2)
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Project Period (FY) |
2017-04-26 – 2019-03-31
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Keywords | Multicellular aging / Nonequilibrium / Dynamical scaling / Cell cycle arrest / Phase transition |
Outline of Annual Research Achievements |
This year, we have achieved great progress in the experimental and theoretical aspects on the nonequilibrium physics in multicellular systems. We conduct an original time-delayed wound healing experiment in which the dynamical scaling of healing efficiency in relation to the waiting time has been discovered. This dynamical scaling of wound healing has a perfect analogy to that of physical relaxations, i.e., physical aging, in complex materials and we have established an asymmetric reaction-diffusion model to explain the biological principles for the emergence of the physical aging on the multicellular level, while proposing a new measurement for bio-age therein. These results are introduced as a synopsis "A new gauge for aging" by the editor of Physics from American Physical Society and published in Physical Review E. On the other hand, the coupling effect of non-mutational homeostasis and mutational adaptation in tumorigenesis is investigated through an agent-based model. It is shown that tumorigenesis is not the a consequence of the accumulation of malicious cells but of the system falling into the tumorigenic homeostasis driven by the Darwinian adaptation. These results are published by Advances in Complex Systems.
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Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Experiments was accomplished as planned while the theoretical exploration has progressed more than expected. Besides the asymmetric reaction-diffusion equation for explaining the multicellular aging, I also developed a stochastic cellular automaton which is analytically solvable with a mean-field approximation for reproducing the evolution of homeostasis towards aging and tumorigenic states without mutations as an active-absorbing phase transition. The control parameters are identified in both models as those affecting the ergodicity of the system. In particular, tumorigenic states of the system are stable spiral nodes but the degenerative states are absorbing states. Normal homeostasis(healthy state),just standing on the border between degenerative states and tumorigenic states, is thence a state of a less stable spiral node with longtime quasi-stable evolution undergoing aging without mutations. These results will be published soon. I also used agent-based modelling to investigate the role of mutation and adaptation in the evolution of multicellular homeostasis and found that the non-mutational phase transitions serve as the "system selection" for the Darwinian adaptation.
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Strategy for Future Research Activity |
The research target next year is focused on the investigation on the ergodicity of multicellular system for engineering multicellular aging in vitro. I with my collaborator in the Medicine Department of University of Tokyo will conduct wound healing experiments with newly equipped cytowatcher, which can monitor the healing processes with high time resolution. Meanwhile, some new designs of the experiments are to pinpoint the control parameter for multicellular aging, which has been proposed by the theory. Various drugs and cell lines will be tested. New paralleled simulations are still supposed to suggest factors related to the control parameter in the multicellular systems in experimennts. Moreover, detailed inspection on the growth of wound edge geometry will be performed with statistical tools. It is supposed to reveal some distinctive cell behaviors during wound healing for different cell lines, initial densities, waiting times and usage of drugs. These results on cell behaviors will be integrated to the theoretical models for multicellular aging for a better approximation to the real systems.
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Research Products
(6 results)