Real-world modeling of life: From DNA to Organoid

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H01877
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 13040:Biophysics, chemical physics and soft matter physics-related
• Research Institution: Doshisha University
• Principal Investigator: Yoshikawa Kenichi 同志社大学, 研究開発推進機構, 客員教授(嘱託研究員) (80110823)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: DNA高次構造転移 / 人工細胞モデル / ミニ臓器創成 / 生命現象の物理 / 非平衡開放系 / 非線形ダイナミクス / 水/水ミクロ相分離 / ゲノムサイズDNA

Outline of Final Research Achievements

Studies have been carried out to uncover the essentials of life, by combining experiments and theoretical analysis. 1) Transitions of higher-order structure of genome-sized DNA were systematically investigated. For example, environmental substances such as polyamines and alcohols cause bimodal effect, promotion and inhibition, on genetic activity depending on their concentrations. Specific changes on the higher-order structure of DNA were clarified through single molecule observations. 2) Self-emergence of cell-like structure were successfully demonstrated through simple experimental procedure by mixing various biomacromolecules such as DNA and skeletal proteins under the solution condition to undergo micro phase-separation. 3) By adapting crowding aqueous solution, it was found that differentiated cells are localized in a specific manner, either in the interior or at the periphery, for micro phase-separated water/water droplets.

Free Research Field

生命物理学、非線形科学

Academic Significance and Societal Importance of the Research Achievements

ゲノムサイズDNAの高次構造変化が、遺伝子活性のon/off変化をもたらすといった、モデル実験での実証は、細胞分化やガンなどでの基本的なメカニズムの解明に今後寄与するものと大いに期待される。高分子混雑溶液でのミクロ相分離により、DNAや骨格タンパクが液滴内に自発的に取り込まれるといった発見は、人工細胞モデルの研究に貢献すると考えられる。さらに、生命の起源などとの関連でも重要な意義がある。多細胞系での空間的組織化が、水/水相分離と直接関連するといった今回の研究での発見は、生物の発生、成長の基本的なメカニズムの解明にも寄与するものと期待される。今後、医学や生命科学の発展に貢献するものと思われる。