Mathematical modeling of virtual human
| Project Area | Science for virtual human development: Organ(s)-on-a-chips reveal systemic metabolic networks |
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| Project/Area Number |
20H05743
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| Research Category |
Grant-in-Aid for Transformative Research Areas (B)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (II)
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
斎藤 輪太郎 慶應義塾大学, 政策・メディア研究科(藤沢), 特任教授 (40348842)
前田 和勲 九州工業大学, 大学院情報工学研究院, 助教 (50631230)
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| Project Period (FY) |
2020-10-02 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥51,480,000 (Direct Cost: ¥39,600,000、Indirect Cost: ¥11,880,000)
Fiscal Year 2022: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2021: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
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| Keywords | 生体医工学関連 / バイオ機能応用およびバイオプロセス工学関連 / 生体医工学 / 生物物理学関連 |
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| Outline of Research at the Start |
本研究は、生体内の細胞・臓器・個体レベルで起きる様々な分子レベルの相互作用を数理モデル化して、その動態を包括的に理解することを目指す。多臓器にわたる全身性疾患の再現や、実証実験による精度検証したモデル化の研究例は少ない。そこで、本研究では、代謝をモデル化し、臓器内で起きる空間的局在や細胞間の物質収支を考慮したヘテロな環境を再現する。多臓器臓器モデル培養系を利用して臓器間の相互作用のモデル化・検証も行う。臓器間連動の再現やそのメカニズムの理解、特に生化学的な合理性の解明を目指す。
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| Outline of Final Research Achievements |
In this study, we implemented mathematical models of the dynamic changes in living systems. To develop and evaluate models related to metabolism, we also performed metabolomic analyses of biological samples in collaboration with other groups. As a model of metabolism at the molecular level, we modeled the interaction of drugs and energy metabolism in hepatocytes. The hepatocytes showed different metabolic patterns based on the zone, i.e., the metabolism of the hepatocytes in the portal vein and the centration vein were different. We also implemented an agent-oriented model of liver fibrosis. Various cells interact to detect dead cells damaged by the toxic compounds and produced collagens. This simulation model was validated by mouse-based experiments. We also modeled the physical and chemical properties of tumor-induced angiogenesis. We added angiopoietins and successfully reproduced the temporal reduction of the new vessels.
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| Academic Significance and Societal Importance of the Research Achievements |
【研究成果の学術的意義】本研究では既知の知見をボトムアップ的に積み上げて数理モデルを開発し、生体内の現象で複雑な要素の定量的な関係性を明らかにすることができた。数理モデルによるシミュレーションで十分なバリデーションを行うことができれば、様々な仮想的な実験を行うことができる。ただし従来のモデル化の方法では、１細胞の精緻化が主体的であったため、本研究では同一細胞でも環境に応じて異なる動態を示すことや、組織レベルで様々な細胞が相互作用することなどを実装した。
【社会的意義】本研究はシステムズ・バイオロジーが目指す数理モデルによる生体の理解を実践した具体的な事例を研究成果として創出することができた。
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Report
(4 results)
Research Products
(76 results)
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[Journal Article] Salivary metabolomics with machine learning for colorectal cancer detection2022
Author(s)
Kuwabara Hiroshi、Katsumata Kenji、Iwabuchi Atsuhiro、Udo Ryutaro、Tago Tomoya、Kasahara Kenta、Mazaki Junichi、Enomoto Masanobu、Ishizaki Tetsuo、Soya Ryoko、Kaneko Miku、Ota Sana、Enomoto Ayame、Soga Tomoyoshi、Tomita Masaru、Sunamura Makoto、Tsuchida Akihiko、Sugimoto Masahiro、Nagakawa Yuichi
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Journal Title
Cancer Science
Volume: 113
Issue: 9
Pages: 3234-3243
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Metabolic profiling of charged metabolites in association with menopausal status in Japanese community-dwelling midlife women: Tsuruoka Metabolomic Cohort Study.2022
Author(s)
Watanabe K, Iida M, Harada S, Kato S, Kuwabara K, Kurihara A, Takeuchi A, Sugiyama D, Okamura T, Suzuki A, Amano K, Hirayama A, Sugimoto M, Soga T, Tomita M, Kobayashi Y, Banno K, Aoki D, Takebayashi T.
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Journal Title
Maturitas
Volume: 155
Pages: 54-62
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Perturbation of monoamine metabolism and enhanced fear responses in mice defective in the regeneration of tetrahydrobiopterin2022
Author(s)
K Miyajima, Y Sudo, S Sanechika, Y Hara, M Horiguchi, F Xu, M Suzuki, S Hara, K Tanda, K Inoue, M Takada, N Yoshioka, H Takebayashi, M Mori-Kojima, M Sugimoto, C Sumi-Ichinose, K Kondo, K Takao, T Miyakawa, H Ichinose
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Journal Title
J Neurochemistry
Volume: 161(2)
Issue: 2
Pages: 129-145
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TGF-β-dependent reprogramming of amino acid metabolism induces epithelial?mesenchymal transition in non-small cell lung cancers2021
Author(s)
Nakasuka Fumie, Tabata Sho, Sakamoto Takeharu, Hirayama Akiyoshi, Ebi Hiromichi, Yamada Tadaaki, Umetsu Ko, Ohishi Maki, Ueno Ayano, Goto Hisatsugu, Sugimoto Masahiro, Nishioka Yasuhiko, Yamada Yasuhiro, Tomita Masaru, Sasaki Atsuo T, Yano Seiji, Soga Tomoyoshi
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Journal Title
Communications Biology
Volume: 4
Issue: 1
Pages: 1-12
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Phase separation and toxicity of C9orf72 poly(PR) depends on alternate distribution of arginine.2021
Author(s)
Chen C, Yamanaka Y, Ueda K, Li P, Miyagi T, Harada Y, Tezuka S, Narumi S, Sugimoto M, Kuroda M, Hayamizu Y, Kanekura K.
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Journal Title
J Cell Biol.
Volume: 220
Issue: 11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells2020
Author(s)
Sho Tanosaki, Shugo Tohyama, Jun Fujita, Hiroki Nakanishi, Takayo Ohto-Nakanishi, Tomohiko Akiyama, Yuika Morita, Yoshikazu Kishino, Marina Okada, Hidenori Tani, Yusuke Soma, Kazuaki Nakajima, Hideaki Kanazawa, Masahiro Sugimoto, Minoru S.H. Ko, Makoto Suematsu, Keiichi Fukuda
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Journal Title
iScience
Volume: 23
Issue: 9
Pages: 101535-101535
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Overexpression of hydroxyproline via EGLN/HIF1A is associated with distant metastasis in pancreatic cancer2020
Author(s)
Naokazu Chiba, Makoto Sunamura, Masashi Nakagawa, Itsuki Koganezawa, Kei Yokozuka, Toshimichi Kobayashi, Kosuke Hikita, Yosuke Ozawa, Masaaki Okihara, Toru Sano, Koichi Tomita, Rina Tsutsui, Masahiro Sugimoto, and Shigeyuki Kawachi
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Journal Title
American Journal of Cancer Research
Volume: 10
Pages: 2570-2581
Related Report
Peer Reviewed / Open Access
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[Journal Article] High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer.2020
Author(s)
Kawashima M, Tokiwa M, Nishimura T, Kawata Y, Sugimoto M, Kataoka TR, Sakurai T, Iwaisako K, Suzuki E, Hagiwara M, Harris AL, Toi M.
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Journal Title
Br J Cancer.
Volume: 122
Issue: 2
Pages: 245-257
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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