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Elucidation of the transcriptional pathways in which amino acids act as a nutritional signal

Research Project

Project/Area Number 23K13900
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 38050:Food sciences-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Mehrazad・Saber Zahra  筑波大学, 医学医療系, 研究員 (50966182)

Project Period (FY) 2023-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2023: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsNutrigenomics / Klf15 / High protein diet
Outline of Research at the Start

Lifestyle diseases benefit from high protein diet (HPD) in a therapeutic and preventive fashion. Transcriptional regulation is considered one of the main contributors of gene expression regulation process that is followed by diet manipulation. In this project, the mechanism of regulatory role of KLF15 on gene expression induced by high protein uptake in the living liver of mice is analyzed by the in vivo promoter analysis method "in vivo Ad-luc method" and the comprehensive transcription factor search "TFEL scan" method.

Outline of Annual Research Achievements

Regarding the Klf15 independent pathway, based on the RNA-Seq analysis of mice fed HPD vs LPD and Klf15 knockout experiment we determined which of the genes involved in amino acid metabolism have altered regulation in response to lack of Klf15 gene while receiving HPD. The genes that their regulation pattern has not been changed are considered Klf15 independent. Regarding in vivo Ad-Luc analysis of candidate genes that estimated promoter site got linked to luciferase reporter gene and formed and Ad-promotrt-Luc plasmid. The adenovirus was applied in the liver of mice fed HPD. The results showed the activity of Ad-promoter-Luc in response to protein intake, and we acquired the genomic region that functions independently from regulatory role of Klf15.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

According to the submitted research plan, progress has been smooth. Regarding KLF15 independent pathways of gene regulation, we determined which of the genes have altered regulation in response to lack of Klf15 gene while receiving HPD. Construction of the Ad-promoter-Luc plasmid was successful. Regarding the in vivo Ad-luc analysis of KLF15 promoter, the experimental methods has been established and the process is expected to go well.

Strategy for Future Research Activity

Regarding the in vivo Ad-luc analysis of KLF15 promoter, the mechanism of KLF15 expression regulation induced by HPD intake will be analyzed by the in vivo Ad-luc method, and the amino acid-responsive enhancer region that recognizes changes in amino acid composition will be identified. Next, we will identify expression regulators that bind to amino acid-responsive enhancers by the TFEL scan method. The molecular interaction will be clarified by trans omics analysis. By proteome analysis, we will proceed with the elucidation of the identified complex centered on the expression regulator and its molecular modification, and at the same time, superimpose the metabolome analysis results of the amino acid metabolites in the nucleus to regulate the expression.

Report

(1 results)
  • 2023 Research-status Report
  • Research Products

    (2 results)

All 2023

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] <scp>GR‐KLF15</scp> pathway controls hepatic lipogenesis during fasting2023

    • Author(s)
      Takeuchi Y, Murayama Y, Aita Y, Mehrazad Saber Z, Karkoutly S, Tao D, Katabami K, Ye C, Shikama A, Masuda Y, Izumida Y, Miyamoto T, Matsuzaka T, Kawakami Y, Shimano H, Yahagi N.
    • Journal Title

      The FEBS Journal

      Volume: 291 Issue: 2 Pages: 259-271

    • DOI

      10.1111/febs.16957

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] in vivo Ad-luc法とTFEL scan法を用いたニュートリゲノミクスへのアプローチ2023

    • Author(s)
      武内謙憲、矢作直也、會田雄一、Mehrazad Saber Zahra、Karkoutly Samia、Tao Duhan、方波見京香、Ye Chen、Wang Xinyu、村山友樹、志鎌明人、升田紫、泉田欣彦、川上康、島野仁
    • Organizer
      第46回日本分子生物学会年会(2023年12月6~8日, 神戸)
    • Related Report
      2023 Research-status Report

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Published: 2023-04-13   Modified: 2024-12-25  

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