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2020 Fiscal Year Final Research Report

Development of a chemical probe for single-cell imaging of FAO pathway and the mechanism of alternation of FAO activity

Research Project

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Project/Area Number 19K15715
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionKyushu University

Principal Investigator

Uchinomiya Shohei  九州大学, 薬学研究院, 助教 (10770498)

Project Period (FY) 2019-04-01 – 2021-03-31
Keywords蛍光イメージング / 代謝経路 / 脂肪酸β酸化 / ケミカルバイオロジー
Outline of Final Research Achievements

It is widely recognized that activities of various metabolic pathways are altered in diseases such as cancer. Therefore, development of chemical probes for measuring activities of metabolic pathways is keenly desired for understanding of disease mechanisms and drug development. In this research, we have developed a new chemical probe for detection of fatty acid beta oxidation (FAO), an important metabolic pathway for energy generation. Using this probe, it was successfully achieved to fluorescently visualize FAO activity in cultured cells and mouse liver tissue. We will apply our probe for chemical proteomics to investigate the alternation of proteome upon the change of FAO activity in cultured cells and mouse liver tissue.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

ガンを始め様々な疾病では代謝活性が大きく変化しているため、標的代謝経路の活性変化を検出する手法の開発は疾病メカニズムの理解や創薬研究に重要である。しかし、従来の同位体標識化合物を用いた測定では細胞集団の平均値しか得られず、代謝研究において重要な不均一性を検出することは困難である。本研究で開発したケミカルプローブはエネルギー生産に重要な脂肪酸β酸化経路を一細胞レベルで蛍光検出可能であり、培養細胞のみならずマウス肝臓サンプルでもβ酸化経路を検出可能であった。今後は本プローブを用いてβ酸化活性変化に伴うプロテオーム変化を解析することで、様々な疾病でのβ酸化が果たす役割を詳細に解析できると期待される。

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Published: 2022-01-27  

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