| Project/Area Number |
21K14752
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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 37030:Chemical biology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
ZHU Hao 京都大学, 工学研究科, 助教 (90874545)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | reactive oxygen species / hydroxyl radical / conditional proteomics / oxidative stress / neurodegeneration / chemical proteomics |
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| Outline of Research at the Start |
Homeostasis of hydroxyl radical in the brain is closely linked with the pathogenesis of neurodegenerative diseases. This research describes a new approach for both imaging and proteomic analysis in neurodegenerative brain, by developing phenol probes for hydroxyl-radical-responsive protein labeling.
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| Outline of Final Research Achievements |
Hydroxyl radical is one member of reactive oxygen species (ROS) that regulates diverse biological and pathological processes in living systems. Due to its high reactivity, hydroxyl radical non-selectively modifies biomolecules which is the onset of many human diseases. This research is developing a new method to decipher hydroxyl radical homeostasis in living systems by hydroxyl-radical-responsive protein labeling, which can unravel the localization and surrounding/associated proteins of hydroxyl radical via fluorescence imaging and proteomics. Chemical probes that can be selectively activated by hydroxyl radical for efficient protein labeling have been identified. Preliminary results have demonstrated that such probe enables hydroxyl-radical-responsive protein labeling in response to endogenously produced hydroxyl radicals in macrophages during immune response. Such progress confirmed the feasibility of the proposed concept of hydroxyl radical conditional protein labeling.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、生体内のヒドロキシルラジカルの網羅的な分析を目指し、蛍光イメージングおよびプロテオミクス用のヒドロキシルラジカル応答性タンパク質標識試薬の最初の例を開発します。これは、細胞のヒドロキシルラジカルの分子メカニズムを解明するのに役立つだけでなく、神経変性疾患などの関連疾患の治療薬標的を発見するための手がかりを提供する可能性があります。
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