| Project/Area Number |
22K14012
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 13040:Biophysics, chemical physics and soft matter physics-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Schnyder Simon 東京大学, 生産技術研究所, 特任助教 (50812616)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2024: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | simulation / cell cycle / active matter / collective behavior |
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| Outline of Research at the Start |
With this project, we aim to advance our understanding of non-volume conserving fluids by studying cell tissue dynamics. We will systematically extend our recently developed hybrid mechanochemical model in three directions: (1) cell motility, (2) apoptosis and (3) friction stemming from hydrodynamic flows. From this this we hope to gain insights into embryogenesis and tumor growth, in particular. We hope to compare our results to those obtained from mechanical models without cell cycle and with experimental data.
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| Outline of Annual Research Achievements |
We have completed a first project in which the cell competition between cell types is studied in detail. For this we extended the model to include programmed cell death (apoptosis) and have it be regulated by the cell cycle. We were then able to study the invasion of one tissue into another as a function of the apoptosis and cell cycle parameters. In particular, we found the invasiveness of a tissue to be enhanced by the ability of cells to resist higher pressures and by lowered apoptotic rates. This was a necessary first step to move towards a better understanding of non-volume conserving fluids by studying cell tissue dynamics. Interestingly, we found that synchronization in the cell division/apoptosis events can emerge, leading to oscillations in pressure and cell-cycle activity.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
My study of non-volume conserving fluids is ongoing. In particular, I am currently in the process of implementing cell motility. I am in contact with two experimental groups who are providing me with data so as to be able to make comparisons with our model.
The results obtained from the first study are promising and have helped attract the attention of one of the two experimental collaborators, who are studying the non-volume conserving expansion of MDCK colonies, while employing new techniques to manipulate the cell’s activity and cell cycle. This makes our simulations an ideal match for their experiments. We are now in the process of using the experiments to calibrate the simulations.
The second experimental cooperation aims to understand more closely the collective dynamics of Dictyostelium discoideum. We are using combining experimental data, my simulations, and a novel machine learning approach.
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| Strategy for Future Research Activity |
Presented with the opportunity to work with these two groups, I adjusted the goals of this project to maximize its impact.
I plan to complete the implementation of cell motility. With the experimental data of the two groups we hope to be able to make substantial progress towards the understanding of the interplay of cell mechanics and cell cycle regulation. With the MDCK system, we aim to understand how the colony expansion is affected by different properties of the cells such as the density, cell cycle activity and how they are distributed across the system. In the second study, we aim to infer the cellular interactions of Dictyostelium discoideum cells by studying how they self-organize.
Furthermore, we plan to be able to study the role of fluid flow in tissues by the end of this project. For this, we plan to implement a mesoscopic coarse grained approach that can account for the conservation of total fluid volume in the system, including the cells and the surrounding medium.
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Report
(1 results)
Research Products
(6 results)
