Elucidation and manipulation of the regulatory mechanisms of cellular functions by metabolic codes

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19064
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 38:Agricultural chemistry and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Miyamoto Takafumi 筑波大学, 医学医療系, 助教 (50740346)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 代謝

Outline of Final Research Achievements

In this study, we defined the fluctuation information of a group of metabolites originating from amino acids as the "metabolite code." Our research aimed to elucidate the mechanisms of sensing the metabolite code and deciphering the information that leads to specific phenotypes. As a result, we were able to identify amino acids that demonstrate coherence and genes that vary due to amino acids. Furthermore, we made progress in establishing cell lines that stably express AMPK and mTORC1 biosensors to visualize the amino acid signals. Ultimately, we successfully established a cell line with stable expression of the AMPK biosensor; however, we prioritized improving the sensitivity of the mTORC1 biosensor.

Free Research Field

栄養学

Academic Significance and Societal Importance of the Research Achievements

本研究により、どのようなアミノ酸が連動して動いているのか、さらにその動きに伴ってどういった遺伝子の発現レベルが変動するのかを明らかにすることができた。ヒトの代謝物は20万種以上あるが、タンパク質の数は19,969 genes/86,245 transcriptsしかない (Nurk et al. Science. 2022)。そのため、細胞がどのようにして膨大な組み合わせからなる栄養素情報の変化を感知・処理しているのかは、未だ謎に包まれている(Efeyan et al. Nature. 2015)。本研究はこの謎を紐解くための基礎データを提供するものである。