Developing a novel force sensor to examine the mechanisms of spindle assembly errors in mammalian oocytes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21404
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: National Institute of Genetics
• Principal Investigator: Shimamoto Yuta 国立遺伝学研究所, 遺伝メカニズム研究系, 准教授 (80409656)
• Co-Investigator(Kenkyū-buntansha): 岩城 光宏 国立研究開発法人理化学研究所, 生命機能科学研究センター, 客員研究員 (30432503)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 紡錘体 / 微小管 / DNAオリガミ / 卵母細胞 / 力学計測

Outline of Final Research Achievements

This research project aimed at developing a novel biophysical tool that enables us to visualize local structural defects and mechanical imbalance within the meiotic spindle, which is assembled in mammalian oocytes for error-free partitioning of chromosomes during cell division. To achieve this, DNA origami-based technology was utilized to create a series of nanometer-sized mechanical springs, which were each flanked by microtubule-binding domains for targeting the spindle. By fluorescent-labeling and polymer-coating, we achieved a specific targeting of the nanospring to microtubules and a stable tracking of its movement within a meiotic cytoplasm.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、未受精卵の内部に形成される染色体分配装置の構造欠陥を可視化することのできるナノサイズの人工素子の開発を行なった。染色体分配装置の形成異常は親細胞から娘細胞への不正確な遺伝情報の継承を招き、胚発生の異常や不妊の主要な原因と考えられている。本開発技術のさらなる精錬により分配装置の形成異常が起こる生物物理学的メカニズムの解明が可能となり、また紡錘体形成異常の早期発見等による新たな治療戦略の創出が期待される。