2011 Fiscal Year Final Research Report
Morphological Profiling in Saccharomyces cerevisiae and Development of high-content imaging techniques
| Project/Area Number |
21310127
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied genomics
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| Research Institution | The University of Tokyo |
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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) |
2009 – 2011
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| Keywords | 出芽酵母 / 機能ゲノム / 細胞周期細胞形態 / 画像解析 |
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| Research Abstract |
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.
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