| 研究課題/領域番号 |
21K15427
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| 研究機関 | 東京大学 |
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研究代表者 |
Jeelani Ghulam 東京大学, 大学院医学系研究科(医学部), 助教 (60468519)
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| 研究期間 (年度) |
2021-04-01 – 2024-03-31
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| キーワード | Entamoeba histolytica / Protozoan parasite / Polyamine / Drug development / Metabolisms |
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| 研究実績の概要 |
Purification and complete characterization of two enzymes involved in polyamine biosynthesis pathway have been completed. Gene silencing and metabolome analysis of one polyamine biosynthesis pathway enzyme (Ornithine decarboxylase) in Entamoeba histolytica has been completed. In this project we have identified one polyamine pathway enzyme which is essential for parasite survival, and since human homologue was absent, therefore this enzyme emerged as a novel drug target candidate
We are going to submit two manuscript one related to glycerol biosynthesis and other related to hexosamine biosynthesis pathway in E. histolytica in this fiscal year. Five manuscripts as a coauthor have been published in the last fiscal year.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We have optimized protein purification protocol using hydrophobic (Butyl-Toyopearl) and anion exchange (MonoQ) columns and enzymatic assay (spermidine synthase) using HPLC, unfortunately we failed to identify the enzyme activity in the amebic lysate. Our repeated attempts to create a transformant in which expression of novel polyamine pathway enzyme repressed by epigenetic gene silencing failed, suggesting the essentiality of the gene.
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| 今後の研究の推進方策 |
To understand the physiological role of the novel polyamine pathway enzyme which we identified in this study we will try other gene knock out approaches.
After transcriptional silencing we will perform phenotypic analysis, RNAseq analysis and then metabolome analysis.
Establish high throughput assay platform for screening Utokyo Drug discovery initiative compounds to identify inhibitors against the novel essential enzyme of polyamine biosynthesis and to determine the frequency, novelty, and potency of compounds with antiamebic activity.
Complete and submit manuscript for publication.
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| 次年度使用額が生じた理由 |
Due to the coronavirus pandemic, the planned use of the budget for conference attendance was not used.
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