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.

药物发现是基于对候选化合物的潜在作用机制和细胞靶标的阐明。我们在酿酒酵母中开发了高含量的成像技术，可以同时分析细胞形状、肌动蛋白和细胞核的形态表型。我们提出了一种新的策略，通过结合表型组数据库和酵母中的高含量成像来识别药物靶点。在这种方法中，我们通过比较化合物诱导的形态特征和酵母突变株的表型来推断候选药物对细胞功能的影响。使用这种方法和四种表征良好的试剂，我们成功地识别了先前已知的化合物的靶基因以及其他与功能相关的细胞通路相关的基因。我们还扩展了对其他细胞结构的形态分析。我们成功地从9个亚细胞结构的数字图像中提取了1111个参数，这些结构包括细胞形状、核DNA、线粒体、肌动蛋白结构、纺锤体、隔膜环、液泡、顺式和反式高尔基体。随着我们研究的进展，系统和全面的形态分析将不可避免地继续取得进展。

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

Multidimensional quantification of subcelluar morphology of Saccharomyces cerevisiae using CalMorph

使用 CalMorph 对酿酒酵母亚细胞形态进行多维定量

• 发表时间: 2009
• 期刊: the high-throughput image-processing program Journal of Biotechnology
• 作者: Negishi T;Nogami S;Ohya Y
• 通讯作者: Ohya Y

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

細胞観察装置、細胞観察方法及びそ のプログラム

细胞观察装置、细胞观察方法及其程序

• 发表时间: 2012

High content, image based screening of drug targets in yeast

基于图像的高内涵酵母药物靶点筛选

• 发表时间: 2010
• 作者: Rintaro Ishii;Yutaka Suzuki;Shinji Kondo;Mariko Okada;Kenji Nishi ,Kumiko Ui-Tei;大矢禎一
• 通讯作者: 大矢禎一