Comprehensive identification of liquid droplet constituents and elucidation of ALS onset mechanism by novel multi-omics analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19356
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Yokohama City University
• Principal Investigator: TAKAHASHI Hidehisa 横浜市立大学, 医学研究科, 教授 (30423544)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 核内凝集体 / 液ー液相分離 / 液滴 / Cajal body / 神経変性疾患

Outline of Final Research Achievements

Despite the absence of membrane structures in the nucleus, the nucleus is compartmentalized into the regions such as euchromatin, heterochromatin, nucleoli, Cajal bodies, and speckles. Recently, it has been clear that these membraneless structures are formed by "liquid droplets" through liquid-liquid phase separation. In this study, we comprehensively identified the components of Cajal bodies by multi-omics analysis using an antibody-based in situ biotinylation method. We attempted to clarify the mechanism of Cajal body formation and how its disruption is involved in the pathogenesis of neurodegenerative diseases including amyotrophic lateral sclerosis.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によってCajal bodyの形成機構とその破綻によるALSなどの神経変性疾患の発症機構との関連が明らかになれば、難治性の神経変性疾患の発症機構の解明に繋がることが期待できる。さらに、Cajal bodyの機能を正常化させることが、神経変性疾患の治療のポイントとなる可能性も考えられる。