Development of mimic biological systems for multimolecular crowding and functional materials working in cells

2021 Fiscal Year Final Research Report

• Project Area: Chemical Approaches for Miscellaneous / Crowding Live Systems
• Project/Area Number: 17H06351
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Konan University
• Principal Investigator: Sugimoto Naoki 甲南大学, 先端生命工学研究所, 教授 (60206430)
• Co-Investigator(Kenkyū-buntansha): 三好 大輔 甲南大学, フロンティアサイエンス学部, 教授 (50388758)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: 分子夾雑 / 細胞模倣実験系 / 生体分子の機能-環境定量相関 / 核酸構造 / 遺伝子発制御

Outline of Final Research Achievements

In this study, we carried out with our research the aim of chemically understanding the role of "multi-molecular crowding environment" and developing techniques to control the gene expression. First, cell-mimicked experimental systems in vitro were created by adding macromolecules and metabolites as co-solutes in aqueous solution. Under the cell-mimicked experimental systems, the structure and function of nucleic acids were analyzed using thermodynamic and kinetic analyses. Moreover, we developed database to predict nucleic acid structure and function in cells. Furthermore, using the database, we analyzed changes in the stability and function of the non-canonical DNA and RNA structures. Moreover, we found that the gene expressions were regulated by structure and stability of nucleic acids. Thus, we proposed “Quantitative Function-Environment Relationship (QFER)” of nucleic acids in the cell and developed methods to regulate gene expression based on QFER.

Free Research Field

物理化学

Academic Significance and Societal Importance of the Research Achievements

核酸の非二重らせん構造の代表例である四重鎖構造は、ヒトゲノムの30万カ所で形成できる可能性がある。さらに、がんや神経疾患関連遺伝子等の発現を制御することも報告され、医学、創薬、診断分野等で注目されている。本領域研究では、核酸の非二重らせん構造、さらには遺伝子発現を、細胞環境因子で制御する技術を開発した。細胞の夾雑環境による遺伝子発現制御システムを開発できたことで、分子夾雑の細胞機能における役割を世界に先駆けて提示ができ、医療、診断、創薬など、実社会に貢献する幅広い応用分野への研究展開が期待される。