| Project/Area Number |
20K08832
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
アブケセーサ イマド 国立研究開発法人理化学研究所, 生命医科学研究センター, 上級研究員 (10749906)
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| Project Period (FY) |
2020-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
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| Keywords | Mycology / Eumycetoma / Galleria mellonella / Antifungal / Madurella mycetomatis / Transcriptomics / Mycetoma / RNA-Seq / Tropical disease |
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| Outline of Research at the Start |
The purpose, scientific significance, and originality of the research project
1- Determine the efficacy of different antifungal agents (fosravuconazole and itraconazole) in an in vivo Madurella mycetomatis grain model in Galleria mellonella larvae 2- Characterize the biological pathways leading to eradication of the pathogen by the drug in pathogen and host 3- Identify molecular markers associated with the response towards the studied antifungal agents
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| Outline of Annual Research Achievements |
In vivo transcriptomics analysis was completed. To determine how a pathogen within a host is responding to treatment, we needed to know first how the pathogen responds to the antifungal agent outside the host (in vitro). We designed an in vitro study to determine how Madurella mycetomatis (Mm) became more tolerant to antifungal agents. We cultured isolate from mycetoma patients in the presence of antifungal agents. We exposed Mm to sub-inhibitory concentrations of itraconazole, terbinafine, ravuconazole, Ampotheracin B, Posaconazole and Olorofim and determine the transcriptomic response towards these drugs. We generated RNA-seq libraries 5 replicates per 3 time points (n=105, including Mm treated with 1%DMSO). The analysis of the in vitro data was completed.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
All planned tasks during 2023 was completed.
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| Strategy for Future Research Activity |
During 2024 our aim was to integrate transcriptomics data from in vivo and in vitro systems. This data then helps us to understand what the main transcriptomic response of the pathogen is to the antifungal agent. In the in vivo situation the response to the antifungal agent is combined with the response of the pathogen to the host. That is a more complicated system. Therefore, combining the in vitro and in vivo response towards the antifungal agents makes it easier to decipher which response is associated with what in this model system. Finally, we are planning to draft a manuscript for submission.
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