Morphological Profiling in Saccharomyces cerevisiae and Development of high-content imaging techniques

酿酒酵母的形态分析和高内涵成像技术的开发

• 批准号: 21310127
• 负责人: OHYA Yoshikazu
• 金额: $ 11.07万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21310127/
• 关键词: 出芽酵母; 機能ゲノム; 細胞周期細胞形態; 画像解析; 薬剤標的; 細胞形態; 細胞周期; 細胞壁; HOG; MAP kinase; シグナル伝達; 紡錘体; M期

Drug discovery are based on elucidation of the potential mechanisms of action and cellular targets of candidate chemical compounds. We developed high-content imaging techniques in Saccharomyces cerevisiae, allowing simultaneous analysis of morphological phenotypes regarding to cell shape, actin and nucleus. We proposed a novel strategy to identify drug targets by combining phenome database and high-content imaging in yeast. In this approach, we infer the cellular functions affected by candidate drugs by comparing morphologic profiles induced by the compounds with the phenotypes of yeast mutants. Using this method and four well-characterized reagents, we successfully identified previously known target genes of the compounds as well as other genes involved with functionally related cellular pathways. We also expanded our morphological analyses on other cellular structures. We succeeded to extract 1,111 parameters from digital images of 9 subcellular structures including cell shape, nuclear DNA, mitochondria, actin structures, spindle pole bodies, septin rings, the vacuole, the cis- and trans-Golgi. With advancements in our study, systematic and comprehensive morphological analyses will inevitably continue to progress.

药物发现基于对候选化合物的潜在作用机制和细胞靶点的阐明。我们开发了酿酒酵母的高内涵成像技术，可以同时分析细胞形状、肌动蛋白和细胞核的形态表型。我们提出了一种结合表型数据库和酵母高内涵成像来识别药物靶点的新策略。在这种方法中，我们通过比较化合物诱导的形态特征与酵母突变体的表型来推断候选药物影响的细胞功能。使用这种方法和四种充分表征的试剂，我们成功地鉴定了先前已知的化合物靶基因以及涉及功能相关细胞途径的其他基因。我们还扩展了对其他细胞结构的形态学分析。我们成功地从 9 个亚细胞结构的数字图像中提取了 1,111 个参数，包括细胞形状、核 DNA、线粒体、肌动蛋白结构、纺锤体极体、隔膜环、液泡、顺式和反式高尔基体。随着我们研究的进步，系统、全面的形态学分析必然会不断进步。

项目成果

Ethanol fermentation driven by elevated expression of the G1 cyclin gene CLN3 in sake yeast.

• DOI: 10.1016/j.jbiosc.2011.08.010
• 发表时间: 2011-12
• 期刊: Journal of bioscience and bioengineering
• 影响因子: 2.8
• 作者: D. Watanabe;Satoru Nogami;Y. Ohya;Y. Kanno;Yan Zhou;T. Akao;H. Shimoi

Knr4 N-terminal domain controls its localization and function during sexual differentiation and vegetative growth

• DOI: 10.1002/yea.1804
• 发表时间: 2010-08-01
• 期刊: YEAST
• 影响因子: 2.6
• 作者: Dagkessamanskaia, Adilia;El Azzouzi, Karim;Martin-Yken, Helene
• 通讯作者: Martin-Yken, Helene

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Image-based systems biology in the budding yeast Saccharomyces cerevisiae

芽殖酵母酿酒酵母中基于图像的系统生物学

• 发表时间: 2012
• 作者: Nguyen Thi Tan Thanh;Dinh Duc Tu;Ngo Duc Thanh;Hoang Minh Toan;Nguyen Quang Vinh;Le Viet Xe;Hideyuki Kamimera;Jun Matsumoto;Yoshikazu Ohya
• 通讯作者: Yoshikazu Ohya

野生Saccharomyces cerevisiaeの形態情報解析

野生酿酒酵母形态信息分析

• 发表时间: 2009
• 作者: Kimihiro Hino;Eigo Shimizu;Kumiko Ui-Tei;里村雄彦;野上識
• 通讯作者: 野上識