Molecular physiological study of impairment in endosome system

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07378
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tohoku University (2019-2020); Institute of Physical and Chemical Research (2017-2018)
• Principal Investigator: ANDO KEIKO 東北大学, 歯学研究科, 准教授 (40221741)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 線虫 / 細胞死 / 重症先天性好中球減少症

Outline of Final Research Achievements

In this study, we focused on vps45 gene, which is one of the causative genes identified in severe congenital neutropenia (SCN). As an model animal, we used the nematode Caenorhabditis elegans (C. elegans) and conducted molecular genetic and molecular physiological studies of vps45. (1) To identify novel genes involved in vps45, we conducted genetic screenings for suppressor mutations of a vps45 mutant and obtained multiple suppressor mutant alleles. (2) We have developed a transgenic animal habouring human vps45 mutations in severe congenital neutropenia. (3) We developed a calcium imaging system to analyze calcium dynamics in apoptotic cells and neural activity in the SCN disease model.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

vps45はエンドソームを介した小胞輸送に働く膜融合制御因子の一つであるが、近年、パーキンソン病などの神経変性疾患においてもエンドソーム輸送の関連遺伝子の変異が多数報告されている。本研究で開発された新規疾患動物モデルは、エンドソーム機能異常を起因とした細胞死の分子メカニズム解明や、神経変性疾患や免疫疾患の創薬を目的とした生体レベルでの薬効評価において優れたツールになることが期待される。