Updated on 2023/09/29

写真a

 
SHIMASAKI Takafumi
 
Organization
Graduate School of Pharmaceutical Sciences Department of Basic Medicinal Sciences Assistant Professor
Graduate School
Graduate School of Pharmaceutical Sciences
Undergraduate School
School of Agricultural Sciences Department of Applied Biosciences
Title
Assistant Professor
Contact information
メールアドレス

Degree 1

  1. 博士(創薬科学) ( 2017.3   名古屋大学 ) 

Research History 1

  1. Nagoya University   School of Agricultural Sciences

    2018.4

Professional Memberships 4

  1. 酵母遺伝学フォーラム

  2. 日本ゲノム微生物学会

  3. 日本分子生物学会

  4. 日本農芸化学会

Committee Memberships 1

  1. 日本農芸化学会中部支部   会計幹事  

    2021.3 - 2023.2   

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    Committee type:Academic society

 

Papers 21

  1. ecl family genes: Factors linking starvation and lifespan extension in Schizosaccharomyces pombe

    Ohtsuka Hokuto, Otsubo Yoko, Shimasaki Takafumi, Yamashita Akira, Aiba Hirofumi

    MOLECULAR MICROBIOLOGY     2023.7

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    Language:English   Publisher:Molecular Microbiology  

    In the fission yeast Schizosaccharomyces pombe, the duration of survival in the stationary phase, termed the chronological lifespan (CLS), is affected by various environmental factors and the corresponding gene activities. The ecl family genes were identified in the genomic region encoding non-coding RNA as positive regulators of CLS in S. pombe, and subsequently shown to encode relatively short proteins. Several studies revealed that ecl family genes respond to various nutritional starvation conditions via different mechanisms, and they are additionally involved in stress resistance, autophagy, sexual differentiation, and cell cycle control. Recent studies reported that Ecl family proteins strongly suppress target of rapamycin complex 1, which is a conserved eukaryotic nutrient-sensing kinase complex that also regulates longevity in a variety of organisms. In this review, we introduce the regulatory mechanisms of Ecl family proteins and discuss their emerging findings.

    DOI: 10.1111/mmi.15134

    Web of Science

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  2. The ecl family gene ecl3(+) is induced by phosphate starvation and contributes to sexual differentiation in fission yeast Reviewed

    Ohtsuka Hokuto, Sakata Hiroki, Kitazaki Yuto, Tada Masanobu, Shimasaki Takafumi, Otsubo Yoko, Maekawa Yasukichi, Kobayashi Mikuto, Imada Kazuki, Yamashita Akira, Aiba Hirofumi

    JOURNAL OF CELL SCIENCE   Vol. 136 ( 6 )   2023.3

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    Language:English   Publisher:Journal of Cell Science  

    In Schizosaccharomyces pombe, ecl family genes are induced by several signals, such as starvation of various nutrients, including sulfur, amino acids and Mg2+, and environmental stress, including heat or oxidative stress. These genes mediate appropriate cellular responses and contribute to the maintenance of cell viability and induction of sexual differentiation. Although this yeast has three ecl family genes with overlapping functions, any environmental conditions that induce ecl3+ remain unidentified. We demonstrate that ecl3+ is induced by phosphate starvation, similar to its chromosomally neighboring genes, pho1+ and pho84+, which respectively encode an extracellular acid phosphatase and an inorganic phosphate transporter. ecl3+ expression was induced by the transcription factor Pho7 and affected by the cyclin-dependent kinase (CDK)-activating kinase Csk1. Phosphate starvation induced G1 arrest and sexual differentiation via ecl family genes. Biochemical analyses suggested that this G1 arrest was mediated by the stabilization of the CDK inhibitor Rum1, which was dependent on ecl family genes. This study shows that ecl family genes are required for appropriate responses to phosphate starvation and provides novel insights into the diversity and similarity of starvation responses.

    DOI: 10.1242/jcs.260759

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  3. Sporulation: A response to starvation in the fission yeast Schizosaccharomyces pombe Reviewed

    Ohtsuka Hokuto, Imada Kazuki, Shimasaki Takafumi, Aiba Hirofumi

    MICROBIOLOGYOPEN   Vol. 11 ( 3 ) page: e1303   2022.6

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    Language:English   Publisher:MicrobiologyOpen  

    The fission yeast Schizosaccharomyces pombe employs two main strategies to adapt to the environment and survive when starved for nutrients. The strategies employ sporulation via sexual differentiation and extension of the chronological lifespan. When a cell is exposed to nutrient starvation in the presence of a cell of the opposite sex, the cells undergo fusion through conjugation and sporulation through meiosis. S. pombe spores are highly resistant to diverse stresses and may survive for a very long time. In this minireview, among the various sexual differentiation processes induced by starvation, we focused on and summarized the findings of the molecular mechanisms of spore formation in fission yeast. Furthermore, comparative measurements of the chronological lifespan of stationary phase cells and G0 cells and the survival period of spore cells revealed that the spore cells survived for a long period, indicating the presence of an effective mechanism for survival. Currently, many molecules involved in sporulation and their functions are being discovered; however, our understanding of these is not complete. Further understanding of spores may not only deepen our comprehension of sexual differentiation but may also provide hints for sustaining life.

    DOI: 10.1002/mbo3.1303

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  4. Tschimganine has different targets for chronological lifespan extension and growth inhibition in fission yeast Reviewed

    Ohtsuka Hokuto, Matsumoto Takuma, Mochida Takahiro, Shimasaki Takafumi, Shibuya Masatoshi, Yamamoto Yoshihiko, Aiba Hirofumi

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   Vol. 86 ( 6 ) page: 775 - 779   2022.5

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    Language:English   Publisher:Bioscience, Biotechnology and Biochemistry  

    Tschimganine inhibits growth and extends the chronological lifespan in Schizosaccharomyces pombe. We synthesized a Tschimganine analog, Mochimganine, which extends the lifespan similar to Tschimganine but exhibits a significantly weaker growth inhibition effect. Based on the comparative analysis of these compounds, we propose that Tschimganine has at least 2 targets: one extends the lifespan and the other inhibits growth.

    DOI: 10.1093/bbb/zbac051

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  5. Response to leucine in Schizosaccharomyces pombe (fission yeast). Reviewed

    Ohtsuka H, Shimasaki T, Aiba H

    FEMS yeast research   Vol. 22 ( 1 )   2022.4

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  6. Characterization of hexose transporter genes in the views of the chronological life span and glucose uptake in fission yeast Reviewed

    Maruyama Teppei, Hayashi Kanako, Matsui Kotaro, Maekawa Yasukichi, Shimasaki Takafumi, Ohtsuka Hokuto, Shigeaki Saitoh, Aiba Hirofumi

    The Journal of General and Applied Microbiology   Vol. 68 ( 6 ) page: 270 - 277   2022

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    Language:English   Publisher:Applied Microbiology, Molecular and Cellular Biosciences Research Foundation  

    <p>Fission yeast, <i>Schizosaccharomyces pombe</i>, possesses eight hexose transporters, Ght1~8. In order to clarify the role of each hexose transporter on glucose uptake, a glucose uptake assay system was established and the actual glucose uptake activity of each hexose transporter-deletion mutant was measured. Under normal growth condition containing 2% glucose, ∆<i>ght5</i> and ∆<i>ght2</i> mutants showed large and small decrease in glucose uptake activity, respectively.<b> </b>On the other hand, the other deletion mutants did not show any decrease in glucose uptake activity indicating that, in the presence of Ght5 and Ght2, the other hexose transporters do not play a significant role in glucose uptake. To understand the relevance between glucose uptake and lifespan regulation, we measured the chronological lifespan of each hexose transporter deletion mutant, and found that only ∆<i>ght5</i> mutant showed a significant lifespan extension. Based on these results we showed that Ght5 is mainly involved in the glucose uptake in <i>Schizosaccharomyces pombe</i>, and suggested that the ∆<i>ght5</i> mutant has prolonged lifespan due to physiological changes similar to calorie restriction.</p>

    DOI: 10.2323/jgam.2022.05.006

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    CiNii Research

  7. Identification of ksg1 mutation showing long-lived phenotype in fission yeast Reviewed

    Matsui Kotaro, Okamoto Keisuke, Hasegawa Tomoka, Ohtsuka Hokuto, Shimasaki Takafumi, Ihara Kunio, Goto Yuhei, Aoki Kazuhiro, Aiba Hirofumi

    GENES TO CELLS   Vol. 26 ( 12 ) page: 967 - 978   2021.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/gtc.12897

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  8. Response to sulfur in Schizosaccharomyces pombe Reviewed

    Ohtsuka Hokuto, Shimasaki Takafumi, Aiba Hirofumi

    FEMS YEAST RESEARCH   Vol. 21 ( 5 )   2021.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/femsyr/foab041

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  9. Extension of chronological lifespan in Schizosaccharomyces pombe Reviewed

    Ohtsuka Hokuto, Shimasaki Takafumi, Aiba Hirofumi

    GENES TO CELLS   Vol. 26 ( 7 ) page: 459 - 473   2021.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/gtc.12854

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  10. Identification of sur2 mutation affecting the lifespan of fission yeast Reviewed

    Kurauchi Tatsuhiro, Matsui Kotaro, Shimasaki Takafumi, Ohtsuka Hokuto, Tsubouchi Satoshi, Ihara Kunio, Tani Motohiro, Aiba Hirofumi

    FEMS MICROBIOLOGY LETTERS   Vol. 368 ( 12 )   2021.6

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/femsle/fnab070

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  11. Genes affecting the extension of chronological lifespan in Schizosaccharomyces pombe (fission yeast) Reviewed

    Ohtsuka Hokuto, Shimasaki Takafumi, Aiba Hirofumi

    MOLECULAR MICROBIOLOGY   Vol. 115 ( 4 ) page: 623 - 642   2021.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/mmi.14627

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  12. Magnesium depletion extends fission yeast lifespan via general amino acid control activation Reviewed

    Ohtsuka Hokuto, Kobayashi Mikuto, Shimasaki Takafumi, Sato Teppei, Akanuma Genki, Kitaura Yasuyuki, Otsubo Yoko, Yamashita Akira, Aiba Hirofumi

    MICROBIOLOGYOPEN   Vol. 10 ( 2 ) page: e1176   2021.3

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    Language:Japanese   Publisher:MicrobiologyOpen  

    Nutrients including glucose, nitrogen, sulfur, zinc, and iron are involved in the regulation of chronological lifespan (CLS) of yeast, which serves as a model of the lifespan of differentiated cells of higher organisms. Herein, we show that magnesium (Mg2+) depletion extends CLS of the fission yeast Schizosaccharomyces pombe through a mechanism involving the Ecl1 gene family. We discovered that ecl1+ expression, which extends CLS, responds to Mg2+ depletion. Therefore, we investigated the underlying intracellular responses. In amino acid auxotrophic strains, Mg2+ depletion robustly induces ecl1+ expression through the activation of the general amino acid control (GAAC) pathway—the equivalent of the amino acid response of mammals. Polysome analysis indicated that the expression of Ecl1 family genes was required for regulating ribosome amount when cells were starved, suggesting that Ecl1 family gene products control the abundance of ribosomes, which contributes to longevity through the activation of the evolutionarily conserved GAAC pathway. The present study extends our understanding of the cellular response to Mg2+ depletion and its influence on the mechanism controlling longevity.

    DOI: 10.1002/mbo3.1176

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  13. Cdc13 (cyclin B) is degraded by autophagy under sulfur depletion in fission yeast Reviewed

    Ohtsuka H, Hatta Y, Hayashi K, Shimasaki T, Otsubo Y, Ito Y, Tsutsui Y, Hattori N, Yamashita A, Murakami H, Aiba H.

    Autophagy Reports     2021

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    Language:English   Publishing type:Research paper (scientific journal)  

  14. Tschimganine has different targets for chronological lifespan extension and growth inhibition in fission yeast Reviewed

    Ohtsuka H*, Matsumoto T*, Mochida T, Shimasaki T, Shibuya M, Yamamoto Aiba H

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY     2021

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    Language:English   Publishing type:Research paper (scientific journal)  

  15. Sulfur depletion induces autophagy through Ecl1 family genes in fission yeast Reviewed

    Shimasaki Takafumi, Okamoto Keisuke, Ohtsuka Hokuto, Aiba Hirofumi

    GENES TO CELLS   Vol. 25 ( 12 ) page: 825 - 830   2020.12

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    Language:Japanese   Publisher:Genes to Cells  

    Autophagy is an intracellular degradation system widely conserved among various species. Autophagy is induced by the depletion of various nutrients, and this degradation mechanism is essential for adaptation to such conditions. In this study, we demonstrated that sulfur depletion induces autophagy in the fission yeast Schizosaccharomyces pombe. Based on the finding that autophagy induced by sulfur depletion was completely abolished in a mutant in which the ecl1, ecl2 and ecl3 genes were deleted (Δecls), we report that these three genes are essential for the induction of autophagy by sulfur depletion. Furthermore, autophagy-defective mutant cells exhibited poor growth and short lifespan (compared with wild-type cells) under the sulfur-depleted condition. These results indicated that the mechanism of autophagy is necessary for the appropriate adaptation to sulfur depletion.

    DOI: 10.1111/gtc.12815

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  16. gas1 mutation extends chronological lifespan via Pmk1 and Sty1 MAPKs in Schizosaccharomyces pombe Reviewed

    Imai Yuki, Shimasaki Takafumi, Enokimura Chihiro, Ohtsuka Hokuto, Tsubouchi Satoshi, Ihara Kunio, Aiba Hirofumi

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   Vol. 84 ( 2 ) page: 330 - 337   2020.2

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/09168451.2019.1676695

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  17. Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1 Reviewed

    Ohtsuka Hokuto, Kato Takanori, Sato Teppei, Shimasaki Takafumi, Kojima Takaaki, Aiba Hirofumi

    MOLECULAR GENETICS AND GENOMICS   Vol. 294 ( 6 ) page: 1499 - 1509   2019.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00438-019-01592-6

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  18. Tschimganine and its derivatives extend the chronological life span of yeast via activation of the Sty1 pathway Reviewed

    Hibi Takahide, Ohtsuka Hokuto, Shimasaki Takafumi, Inui Shougo, Shibuya Masatoshi, Tatsukawa Hideki, Kanie Kei, Yamamoto Yoshihiko, Aiba Hirofumi

    GENES TO CELLS   Vol. 23 ( 8 ) page: 620 - 637   2018.8

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/gtc.12604

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  19. Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome Reviewed

    Ohtsuka Hokuto, Takinami Masahiro, Shimasaki Takafumi, Hibi Takahide, Murakami Hiroshi, Aiba Hirofumi

    MOLECULAR MICROBIOLOGY   Vol. 105 ( 1 ) page: 84 - 97   2017.7

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/mmi.13686

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  20. Ecl1 is a zinc-binding protein involved in the zinc-limitation-dependent extension of chronological life span in fission yeast Reviewed

    Shimasaki Takafumi, Ohtsuka Hokuto, Naito Chikako, Azuma Kenko, Tenno Takeshi, Hiroaki Hidekazu, Murakami Hiroshi, Aiba Hirofumi

    MOLECULAR GENETICS AND GENOMICS   Vol. 292 ( 2 ) page: 475 - 481   2017.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00438-016-1285-x

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  21. Ecl1 is activated by the transcription factor Atf1 in response to H2O2 stress in Schizosaccharomyces pombe Reviewed

        2014.4

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Presentations 18

  1. 分裂酵母における(Ecl1ファミリー遺伝子を介した)硫黄枯渇による細胞小型化の解析

    八田佳子, 筒井優, 服部允赳, 島崎崇史, 大塚北斗, 饗場浩文

    第42回 日本分子生物学会年会  

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    Event date: 2020.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:福岡   Country:Japan  

  2. Mg枯渇時における分裂酵母の経時寿命延長因子Ecl1 Family遺伝子の解析

    小林未来登, 佐藤哲平, 大塚北斗, 島崎嵩史, 饗場浩文

    日本農芸化学会中部支部第187回例会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  3. 分裂酵母におけるGhtファミリータンパク質の欠失がグルコース取り込みと寿命へ与える影響の解析

    丸山哲平、林可奈子、島崎嵩史、大塚北斗、齋藤成昭、饗場浩文

    日本農芸化学会中部支部第187回例会 

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  4. 分裂酵母におけるTschimganineの作用機構の解析

    松本拓磨、大塚北斗、持田尚宏、島崎嵩史、澁谷正俊、山本芳彦、饗場浩文

    日本農芸化学会中部支部第187回例会 

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  5. 分裂酵母における硫黄枯渇制限下での細胞小型化の解析

    八田佳子、筒井優、服部允赳、島崎嵩史、大塚北斗、饗場浩文

    日本農芸化学会中部支部第187回例会 

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  6. 分裂酵母において硫黄枯渇はEcl1ファミリー遺伝子依存的にオートファジーを誘導する

    島崎嵩史, 岡本啓佑, 大塚北斗, 饗場浩文

    酵母遺伝学フォーラム第53回研究報告会 

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    Event date: 2020.9

    Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  7. 経時寿命が延長する分裂酵母変異株のスクリーニングと新規寿命関連因子の同定

    松井滉太朗、岡本啓佑、長谷川朋香、島崎嵩史、大塚北斗、井原邦夫、後藤祐平、青木一洋、饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  8. Mg枯渇時における分裂酵母の経時寿命延長因子Ecl1ファミリー遺伝子の解析

    小林未来登, 佐藤哲平, 大塚北斗, 島崎嵩史, 饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  9. 分裂酵母における硫黄枯渇による細胞小型化の解析

    八田佳子、筒井優、服部允赳、大塚北斗、島崎嵩史、饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  10. 分裂酵母におけるTschimganineの作用機構の解析

    松本拓磨、大塚北斗、持田尚宏、島崎嵩史、山本芳彦、饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  11. 分裂酵母におけるアミノ酸枯渇応答機構の解析

    島崎嵩史、大塚北斗、佐藤哲平、赤沼元気、饗場浩文

    第14回 日本ゲノム微生物学会年会  

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    Event date: 2020.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  12. 分裂酵母におけるTschimganineの作用機構の解析

    持田尚宏、大塚北斗、松本拓磨、島崎嵩史、澁谷正俊、山本芳彦、饗場浩文

    第14回 日本ゲノム微生物学会年会  

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    Event date: 2020.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  13. 経時寿命が延長する分裂酵母変異株のスクリーニングと新規寿命関連因子の同定

    松井滉太朗、岡本啓佑、長谷川朋香、島崎嵩史、大塚北斗、井原邦夫、中村彰伸、後藤祐平、青木一洋、饗場浩文

    第14回 日本ゲノム微生物学会年会  

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    Event date: 2020.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  14. 分裂酵母における硫黄枯渇と細胞応答

    筒井優、服部允赳、八田佳子、大塚北斗、島崎嵩史、饗場浩文

    第14回 日本ゲノム微生物学会年会 

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    Event date: 2020.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  15. マグネシウム枯渇条件下における分裂酵母の経時寿命延長因子Ecl1 family遺伝子の解析

    小林未来登, 佐藤哲平, 大塚北斗, 島崎嵩史, 饗場浩文

    第42回 日本分子生物学会年会  

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    Event date: 2019.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:福岡   Country:Japan  

  16. アミノ酸枯渇に応答する分裂酵母の経時寿命延長因子Ecl1 Family 遺伝子の解析

    佐藤哲平、大塚北斗、加藤敬典、島崎嵩史、饗場浩文

    酵母遺伝学フォーラム第52回研究報告会  

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    Event date: 2019.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:静岡市清水文化会館マリナート  

  17. 分裂酵母におけるgas1 変異による寿命延長機構の解析

    島崎嵩史、今井優希、榎村千尋、大塚北斗、井原邦夫、饗場浩文

    酵母遺伝学フォーラム第52回研究報告会 

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    Event date: 2019.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:静岡市清水文化会館マリナート   Country:Japan  

  18. Leucine depletion extends the lifespans of fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. International conference

    Hirofumi Aiba, Hokuto Ohtsuka, Takanori Kato, Teppei Sato, and Takafumi Shimasaki

    The 10 th International Fission Yeast Meeting  

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    Event date: 2019.7

    Language:English   Presentation type:Poster presentation  

    Venue:Barcelona, Spain   Country:Spain  

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KAKENHI (Grants-in-Aid for Scientific Research) 2

  1. 細胞周期制御に関わる新規寿命関連因子の機能解明

    Grant number:23K13868  2023.4 - 2025.3

    科学研究費助成事業  若手研究

    島崎 嵩史

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    過去に新規寿命制御因子の同定を目的として長寿命変異株のスクリーニングが行われ、解析の対象であるnnk1変異株が取得された。全ゲノムシークエンス解析の結果、機能未知の遺伝子nnk1+において変異(nnk1-35変異)が確認され、この変異が長寿命の表現型の原因であることが明らかとなった。nnk1+遺伝子は生育に必須であり、nnk1変異株も高温感受性の表現型を示すが、解析の結果、Nnk1タンパク質が寿命制御だけでなく細胞周期の制御に関与することが示唆された。本研究ではこのNnk1タンパク質の生理学的機能を明らかにし、Nnk1タンパク質による寿命制御および細胞周期制御メカニズムの解明を目指す。

  2. 分裂酵母における新規キナーゼNnk1による寿命制御機構の解明

    Grant number:21K14769  2021.4 - 2023.3

    科学研究費助成事業  若手研究

    島崎 嵩史

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    本研究では、分裂酵母における新規の寿命制御因子であるNnk1タンパク質の生理学的機能、およびその寿命制御メカニズムの解明を行う。分裂酵母は基本的な細胞内メカニズムが高等生物と類似しており、種々の寿命制御因子(カロリー制限応答、PKA、TORなど)も保存されており、優れた寿命研究モデルである。分裂酵母におけるNnk1タンパク質による寿命制御メカニズムの解明を通して、高等生物の寿命制御の理解に寄与する知見を得ることを目指す。
    本研究では、分裂酵母における新規寿命関連因子Nnk1による寿命制御機構の解明を目指し、解析を行っている。nnk1+遺伝子は分裂酵母の生育に必須であり、コードしているタンパク質内にはキナーゼドメインと予測される配列が存在しているが、Nnk1タンパク質の基質や生理学的機能については今のところ明らかになっていない。しかしながら過去に、新規寿命制御因子の同定を目的とした長寿命変異株のスクリーニングが行われ、nnk1+遺伝子において生じた変異(nnk1-35変異)が経時寿命の延長を引き起こすことが明らかとなっている。本研究ではこのNnk1タンパク質の標的基質および下流で機能する因子を明らかにし、Nnk1タンパク質による未知の寿命制御機構の解明を目指し、より高等な生物種の寿命制御機構の解明に寄与する可能性のある新たな知見を得ることを目的としている。
    解析にあたり、まずは下流因子の探索スクリーニングに必要なnnk1高温感受性変異株の取得を試みた。当初の予定では、nnk1遺伝子の近傍にカナマイシン耐性遺伝子(kanR)を導入し、その株に対してエラープローンPCRによる変異の導入を行う予定だったが、nnk1-35変異の近傍にkanRを導入した株が顕著な高温感受性を示したため、この株にプラスミドゲノムライブラリーを導入し、スクリーニングを実施中である。リン酸化基質の同定に関しては、Nnk1タンパク質を過剰発現するプラスミドを作製後に分裂酵母に導入し、この株を用いてリン酸化プロテオミクス解析に向けての条件検討などを行なっている。
    当初はnnk1高温感受性変異株の作製を試み、これが難航していたが、作製したnnk1-35-kanR変異株に顕著な高温感受性が観察され、ゲノムライブラリープラスミドを導入することでこの表現型を回復する因子のスクリーニングを進めている。現在、既にこの高温感受性を回復した株がいくつか取得されており、表現型の回復に関与する遺伝子の同定をシーケンス解析によって進めている最中である。Nnk1タンパク質のリン酸化基質の同定に関しても、当初はタグ付きのNnk1タンパク質を分裂酵母の細胞内に発現させ、プルダウンを行なう手順で実施する予定であったが、Nnk1タンパク質のプルダウンが難航したため、Nnk1タンパク質を過剰発現した際に、リン酸化レベルが上昇したタンパク質を網羅的に解析する方針に転換している。現在までに、このリン酸化プロテオミクス解析に必要なNnk1タンパク質を過剰量発現可能なプラスミドの作製に成功し、実際に分裂酵母内で過剰量発現することを確認済みである。
    今後は引き続き、ゲノムライブラリーを用いたnnk1-35-kanR変異株の温度感受性を相補する因子の取得と同定を目指す。リン酸化基質の同定に関しては、Nnk1タンパク質を過剰発現した際にコントロールと比較してリン酸化レベルが上昇しているタンパク質を、質量分析を用いて網羅的に解析する。これら2つの網羅的解析から、Nnk1タンパク質のリン酸化基質、及び下流因子を絞り込み、Nnk1タンパク質の生理学的機能や寿命制御メカニズムを明らかにする予定である。

 

Teaching Experience (On-campus) 12

  1. Biological Science Research Course (Advanced Course)

    2021

  2. Specific Lecture for Advanced Pharmaceutical Sciences

    2021

  3. Seminar in Life Science IIC

    2021

  4. Seminar in Life Science IIA

    2021

  5. Biological Science Research Course

    2021

  6. Seminar in Biological Science ⅠB

    2021

  7. Seminar in Biological Science ⅠA

    2021

  8. Seminar in Life Science IID

    2021

  9. Seminar in Life Science IIB

    2021

  10. Basic Training for Crossover Research Course

    2021

  11. Basic Training for Crossover Research

    2021

  12. 応用生命科学実験実習

    2020

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