成果報告書詳細
管理番号20140000000151
タイトル*平成25年度中間年報 「後天的ゲノム修飾のメカニズムを活用した創薬基盤技術開発」(国立大学法人東京大学、エピゲノム技術研究組合)
公開日2014/8/8
報告書年度2013 - 2013
委託先名国立大学法人東京大学 エピゲノム技術研究組合
プロジェクト番号P10005
部署名バイオテクノロジー・医療技術部
和文要約
英文要約Title: Technology development for drug discovery platform based on the epigenetic mechanism (FY2010-FY2015) FY2013 Annual Report
 
(1) Technology development for comprehensive analysis of epigenetic modifications: We optimized the whole-genome and base-resolution analysis of cytosine methylation, WGBS and PBAT. We optimized the method to detect cytosine hydroxymethylation in a one base resolution, TAB-sequencing. We started to analyze H3 tail using newly installed Tribrid mass spectrometer (Orbitrap-Fusion) with high speed and high resolution MS/MS. We started to develop software to determine exact sites of histone modifications. We have enhanced sensitivity by adapting ion source to Orbitrap, which we had developed for SRM previously. (2) Development of data mining platform to discover the relationship between epigenetic modifications and the disease: We selected the candidate markers that are commonly methylated among multiple types of cancers or are aberrantly methylated in a cancer-type specific manner by using epigenotyping microarrays and validated them for diagnostic application using circulating blood DNA in patients. Newly developed technologies for epigenomic analysis have been applied to examine clinical specimens, and revealed aberrant profiles of epigenetic marks, such as DNA demethylation and chromatin accessibility in hepatocellular carcinoma and DNA demethylation in hematological malignancies. (3) Exploratory experimental study: We have developed a method to identify proteins that reads a modification that was detected in H4 tail analysis during cell cycle. Drug screening with MS has been speeded up by 10 times using a newly installed MALD-TOFMS. We have established TR-FRET based screening for some target enzyme and carried out natural compound screening. We are trying to co-crystalize the drugs screened and the enzymes for X-ray crystallography.
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