| Project/Area Number |
21K15427
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Entamoeba histolytica / polyamine pathway / Protozoan Parasite / Metabolism / Drug development / Protozoan parasite / Polyamine / Metabolisms / Drug developement |
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| Outline of Research at the Start |
Metabolic pathways and specific enzymes that are selectively present in pathogens and essential for survival are ideal targets for chemotherapy. The polyamine synthesis pathway has been proven to be rational useful target. The human parasite, Entamoeba histolytica,lacks the conventional enzymes involved in polyamine biosynthesis. However, our previous metabolome analysis revealed that this parasite produces polyamines and secretes them extracellularly. This study aims to elucidate a novel polyamine synthesis pathway that has evolved peculiar to this parasites.
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| Outline of Final Research Achievements |
In this project, we purified and characterized two enzymes involved in the polyamine biosynthesis pathway in E. histolytica. We conducted gene silencing and metabolome analysis of the polyamine biosynthesis pathway enzymes (Ornithine decarboxylase and a novel decarboxylase) in Entamoeba histolytica. We identified one polyamine pathway enzyme essential for parasite survival, which lacked a human homologue, making it a novel drug target candidate. We are optimizing a high-throughput screening assay against the novel decarboxylase identified in this study, aiming to find inhibitors that target this essential enzyme and inhibit the growth of the parasite.
In the last fiscal year, we published one manuscript and co-authored five manuscripts. Additionally, two manuscripts, one related to the Riboflavin pathway and the other related to the hexosamine biosynthesis pathway in E. histolytica, are currently under review. We are now compiling the data and preparing the manuscript for submission.
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| Academic Significance and Societal Importance of the Research Achievements |
Our research on drug development against protozoan parasites is significant. I identified enzymes crucial for parasite survival, potentially leading to new treatments. Socially, this work addresses global health challenges, offering new compounds to improve treatments and reduce disease burden.
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