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

Research Project

Project/Area Number 21K19064
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionUniversity 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
Project Status Completed (Fiscal Year 2022)
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)
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。

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.

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。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (17 results)

All 2023 2022 2021

All Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Morphological and functional adaptation of pancreatic islet blood vessels to insulin resistance is impaired in diabetic db/db mice2022

    • Author(s)
      Okajima Yuka、Matsuzaka Takashi、Miyazaki Shun、Motomura Kaori、Ohno Hiroshi、Sharma Rahul、Shimura Takuya、Istiqamah Nurani、Han Song-iee、Mizunoe Yuhei、Osaki Yoshinori、Iwasaki Hitoshi、Yatoh Shigeru、Suzuki Hiroaki、Sone Hirohito、Miyamoto Takafumi、Aita Yuichi、Takeuchi Yoshinori、Sekiya Motohiro、Shimano Hitoshi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1868 Issue: 4 Pages: 166339-166339

    • DOI

      10.1016/j.bbadis.2022.166339

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ELOVL5-mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma2022

    • Author(s)
      Nitta Satoshi、Kandori Shuya、Tanaka Ken、Sakka Shotaro、Siga Masanobu、Nagumo Yoshiyuki、Negoro Hiromitsu、Kojima Takahiro、Mathis Bryan J.、Shimazui Toru、Miyamoto Takafumi、Matsuzaka Takashi、Shimano Hitoshi、Nishiyama Hiroyuki
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 8 Pages: 2738-2752

    • DOI

      10.1111/cas.15454

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heat shock‐induced heme oxygenase‐1 expression in a mouse hepatoma cell line is dependent on <scp>HSF1</scp> and modified by <scp>NRF2</scp> and <scp>BACH1</scp>2022

    • Author(s)
      Inouye Sachiye、Kubo Takanori、Miyamoto Takafumi、Iyoda Takuya、Okita Naoyuki、Akagi Reiko
    • Journal Title

      Genes to Cells

      Volume: 27 Issue: 12 Pages: 719-730

    • DOI

      10.1111/gtc.12986

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 323 Issue: 6 Pages: 627-639

    • DOI

      10.1152/ajpgi.00090.2022

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A case of NASH with genetic predisposition successfully treated with an SGLT2 inhibitor: a possible involvement of mitochondrial dysfunction.2022

    • Author(s)
      Nakajima R, Sekiya M, Furuta Y, Miyamoto T, Sato M, Fukuda K, et, al.
    • Journal Title

      Endocrinol Diabetes Metab Case Rep.

      Volume: 22 Pages: 0368-0368

    • DOI

      10.1530/edm-22-0368

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Starvation‐induced transcription factor CREBH negatively governs body growth by controlling GH signaling2021

    • Author(s)
      Nakagawa Yoshimi、Kumagai Kae、Han Song‐iee、Mizunoe Yuhei、Araki Masaya、Mizuno Seiya、Ohno Hiroshi、Matsuo Kazuya、Yamada Yasunari、Kim Jun‐dal、Miyamoto Takafumi、Sekiya Motohiro、Konishi Morichika、Itoh Nobuyuki、Matsuzaka Takashi、Takahashi Satoru、Sone Hirohito、Shimano Hitoshi
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 6 Pages: 21663-21663

    • DOI

      10.1096/fj.202002784rr

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CtBP2 confers protection against oxidative stress through interactions with NRF1 and NRF22021

    • Author(s)
      Kainoh Kenta、Takano Ryo、Sekiya Motohiro、Saito Kenji、Sugasawa Takehito、Ma Yang、Murayama Yuki、Sugano Yoko、Osaki Yoshinori、Iwasaki Hitoshi、Takeuchi Yoshinori、Yahagi Naoya、Suzuki Hiroaki、Miyamoto Takafumi、Nakagawa Yoshimi、Matsuzaka Takashi、Shimano Hitoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 562 Pages: 146-153

    • DOI

      10.1016/j.bbrc.2021.05.069

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heme oxygenase-1 induction by heat shock in rat hepatoma cell line is regulated by the coordinated function of HSF1, NRF2 and BACH12021

    • Author(s)
      Akagi Reiko、Kubo Takanori、Hatori Yuta、Miyamoto Takafumi、Inouye Sachiye
    • Journal Title

      The Journal of Biochemistry

      Volume: 170 Issue: 4 Pages: 501-510

    • DOI

      10.1093/jb/mvab065

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protocol for rapid manipulation of mitochondrial morphology in living cells using inducible counter mitochondrial morphology (iCMM)2021

    • Author(s)
      Miyamoto Takafumi、Han Song-Iee、Shimano Hitoshi
    • Journal Title

      STAR Protocols

      Volume: 2 Issue: 3 Pages: 100721-100721

    • DOI

      10.1016/j.xpro.2021.100721

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Cell Reports Methods

      Volume: 1 Issue: 4 Pages: 100052-100052

    • DOI

      10.1016/j.crmeth.2021.100052

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High protein diet-induced metabolic changes are transcriptionally regulated via KLF15-dependent and independent pathways2021

    • Author(s)
      Mehrazad Saber Zahra、Takeuchi Yoshinori、Sawada Yoshikazu、Aita Yuichi、Ho Man Hei、Karkoutly Samia、Tao Duhan、Katabami Kyoka、Ye Chen、Murayama Yuki、Shikama Akito、Masuda Yukari、Izumida Yoshihiko、Miyamoto Takafumi、Matsuzaka Takashi、Sugasawa Takehito、Takekoshi Kazuhiro、Kawakami Yasushi、Shimano Hitoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 582 Pages: 35-42

    • DOI

      10.1016/j.bbrc.2021.10.027

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis2021

    • Author(s)
      Sekiya Motohiro、Kainoh Kenta、Sugasawa Takehito、Yoshino Ryunosuke、Hirokawa Takatsugu、Tokiwa Hiroaki、Nakano Shogo、Nagatoishi Satoru、Tsumoto Kouhei、Takeuchi Yoshinori、Miyamoto Takafumi、Matsuzaka Takashi、Shimano Hitoshi
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 1-19

    • DOI

      10.1038/s41467-021-26638-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ELOVL2 promotes cancer progression by inhibiting cell apoptosis in renal cell carcinoma2021

    • Author(s)
      Tanaka Ken、Kandori Shuya、Sakka Shotaro、Nitta Satoshi、Tanuma Kozaburo、Shiga Masanobu、Nagumo Yoshiyuki、Negoro Hiromitsu、Kojima Takahiro、Mathis Bryan、Shimazui Toru、Watanabe Makoto、Sato Taka-Aki、Miyamoto Takafumi、Matsuzaka Takashi、Shimano Hitoshi、Nishiyama Hiroyuki
    • Journal Title

      Oncology Reports

      Volume: 47 Issue: 2 Pages: 23-23

    • DOI

      10.3892/or.2021.8234

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin2021

    • Author(s)
      Takeuchi Yoshinori、Yahagi Naoya、Aita Yuichi、Mehrazad-Saber Zahra、Ho Man Hei、Huyan Yiren、Murayama Yuki、Shikama Akito、Masuda Yukari、Izumida Yoshihiko、Miyamoto Takafumi、Matsuzaka Takashi、Kawakami Yasushi、Shimano Hitoshi
    • Journal Title

      iScience

      Volume: 24 Issue: 12 Pages: 103446-103446

    • DOI

      10.1016/j.isci.2021.103446

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Rapid Manipulation of Mitochondrial Morphology in a Living Cell with iCMM2023

    • Author(s)
      Takafumi Miyamoto
    • Organizer
      Gordon Research Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] イメージングメタアナリシスの現状と課題2022

    • Author(s)
      宮本崇史
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 情報因子としてのオルガネラ形態に対する理解と制御2022

    • Author(s)
      宮本崇史
    • Organizer
      第19回糖鎖科学コンソーシアムシンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited

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Published: 2021-07-13   Modified: 2024-01-30  

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