Global study of haploinsufficient genes in Saccharomyces cerevisiae
Project/Area Number |
19H03205
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 43050:Genome biology-related
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Research Institution | The University of Tokyo |
Principal Investigator |
Ohya Yoshikazu 東京大学, 大学院新領域創成科学研究科, 教授 (20183767)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | ハプロ不全性 / 出芽酵母 / CCTシャペロニン複合体 / 不十分量仮説 / CalMorph / 形態解析 / 細胞形態 / シャペロニンCCT / 形態表現型 / フェノーム |
Outline of Research at the Start |
ハプロ不全は二倍体生物のヘテロ接合体で機能欠損側の表現型が現れる遺伝現象であるが、そのメカニズムはほとんど明らかになっていなかった。今までハプロ不全は稀に見られる現象であると考えられてきたが、研究代表者らは最近出芽酵母変異株において半数以上の必須遺伝子ヘテロ破壊株が形態的にハプロ不全性を示すことを明らかにした。そこで本研究ではまず、形態的にハプロ不全性が生じる分子メカニズムを出芽酵母で網羅的に解析する。ハプロ不全性が起こりやすくなる条件、起こりにくくなる条件を明らかにする。この知見を踏まえて形態的なハプロ不全性を利用した化合物の細胞内標的方法を開発する。
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Outline of Final Research Achievements |
The purpose of this study is to elucidate the molecular mechanism of haploinsufficiency in essential genes of Saccharomyces cerevisiae. Using all 8 genes (TCT1, CCT2-CCT8) that encode the subunits of the chaperonin CCT complex essential for cell proliferation, it was examined whether overexpression of the genes shows the same morphological phenotypes as haploinsufficient morphological phenotypes. As a result, no significant morphological change was observed even after overexpression. This result denied the balance hypothesis that the same morphological phenotype appears whether the gene expression level was increased or decreased, and supported the insufficient amount hypothesis.
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Academic Significance and Societal Importance of the Research Achievements |
ヒト遺伝病データベース(OMIM)によると、ハプロ不全性様式のヒトの優性遺伝病は現在700件以上の登録がされている。ヒトゲノムの解析からハプロ不全性遺伝子に対する興味が高まる中で、本研究では遺伝子操作と表現型解析が容易に行える出芽酵母の利点を生かしてハプロ不全性のメカニズムに実験的にアプローチした。得られた結果からは、ハプロ不全性のメカニズムとして不十分量仮説が支持されるようになり、ハプロ不全様式の優性遺伝病の理解に役立つ知見が得られた。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Poacic acid, a β-1,3-glucan-binding antifungal agent, inhibits cell-wall remodeling and activates transcriptional responses regulated by the cell-wall integrity and high-osmolarity glycerol pathways in yeast.2021
Author(s)
Garcia R, Itto-Nakama K, Rodriguez-Pena JM, Chen X, Sanz AB, de Lorenzo A, Pavon-Verges M, Kubo K, Ohnuki S, Nombela C, Popolo L, Ohya Y, Arroyo J.
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Journal Title
FASEB J.
Volume: 10
Issue: 9
Pages: 1299-1299
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genome Editing to Generate Sake Yeast Strains with Eight Mutations That Confer Excellent Brewing Characteristics.2021
Author(s)
Chadani T, Ohnuki S, Isogai A, Goshima T, Kashima M, Ghanegolmohammadi F, Nishi T, Hirata D, Watanabe D, Kitamoto K, Akao T, Ohya Y.
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Journal Title
Cells
Volume: 10
Issue: 6
Pages: 1299-1299
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sequentially addressable dielectrophoretic array for high-throughput sorting of large-volume biological compartments2020
Author(s)
A Isozaki, Y Nakagawa, M H Loo, Y Shibata, N Tanaka, D L Setyaningrum, J-W Park, Y Shirasaki, H Mikami, D Huang, H Tsoi, C T Riche, T Ota, H Miwa, Y Kanda, T Ito, K Yamada, O Iwata, K Suzuki, S Ohnuki, Y Ohya, Y Kato, T Hasunuma, S Matsusaka, M Yamagishi, M Yazawa, S Uemura, K Nagasawa, H Watarai, D Di Carlo, K Goda
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Journal Title
Science Advances
Volume: 29
Issue: 22
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 6 Virtual-freezing fluorescence imaging flow cytometry.2020
Author(s)
Mikami H, Kawaguchi M, Huang CJ, Matsumura H, Sugimura T, Huang K, Lei C, Ueno S, Miura T, Ito T, Nagasawa K, Maeno T, Watarai H, Yamagishi M, Uemura S, Ohnuki S, Ohya Y, Kurokawa H, Matsusaka S, Sun CW, Ozeki Y, Goda K.
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Journal Title
Nat Commun.
Volume: 6
Issue: 1
Pages: 1162-1162
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genome editing to generate nonfoam-forming sake yeast strains2019
Author(s)
Shinsuke Ohnuki, Mao Kashima, Toshikazu Yamada, Farzan Ghanegolmohammadi, Yan Zhou, Tetsuya Goshima, Jun-ichi Maruyama, Katsuhiko Kitamoto, Dai Hirata, Takeshi Akao, Yoshikazu Ohya
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Journal Title
Bioscience, Biotechnology, and Biochemistry
Volume: 83
Issue: 8
Pages: 1583-1593
DOI
Related Report
Peer Reviewed
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