Elucidation and manipulation of the regulatory mechanisms of cellular functions by metabolic codes
Project/Area Number |
21K19064
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 38:Agricultural chemistry and related fields
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Research Institution | University of Tsukuba |
Principal Investigator |
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Project Period (FY) |
2021-07-09 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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Keywords | 代謝 / アミノ酸 / 時空間的活性ダイナミクス / 栄養学 / 合成生物学 |
Outline of Research at the Start |
本研究では細胞内の代謝物質が創り出す様々な情報を『代謝物質コード』として定義し、その代謝物質コードを感知・解読するメカニズムや、その結果として特定の表現型に至る背景機序を明らかにすると共に、それを自在にコントロールすることができる手法を開発することで、代謝物質コードの理解と制御を試みる。
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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.
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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。
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Hepatocyte- or macrophage-specific SREBP-1a deficiency in mice exacerbates methionine- and choline-deficient diet-induced nonalcoholic fatty liver disease.2022
Author(s)
Araki M, Nakagawa Y, Saito H, Yamada Y, Han SI, Mizunoe Y, Ohno H, Miyamoto T, Sekiya M, Matsuzaka T, Sone H, Shimano H.
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Journal Title
Am J Physiol Gastrointest Liver Physiol
Volume: 323
Issue: 6
Pages: 627-639
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Rapid manipulation of mitochondrial morphology in a living cell with iCMM2021
Author(s)
Miyamoto Takafumi、Uosaki Hideki、Mizunoe Yuhei、Han Song-Iee、Goto Satoi、Yamanaka Daisuke、Masuda Masato、Yoneyama Yosuke、Nakamura Hideki、Hattori Naoko、Takeuchi Yoshinori、Ohno Hiroshi、Sekiya Motohiro、Matsuzaka Takashi、Hakuno Fumihiko、Takahashi Shin-Ichiro、Yahagi Naoya、Ito Koichi、Shimano Hitoshi
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Journal Title
Cell Reports Methods
Volume: 1
Issue: 4
Pages: 100052-100052
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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