| Project/Area Number |
19K15695
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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 37010:Bio-related chemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
Maity Basudev 東京工業大学, 生命理工学院, 特任助教 (60815421)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | Ferritin / Amyloid beta oligomer / High-speed AFM / Ferritin cage / Alpha-synuclein oligomer / Dynamics / Alpha-synuclein / Nanoscale dynamics |
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| Outline of Research at the Start |
The proposed research plan is outlined in the three following parts.
(a) Preparation of the α-syn fused ferritin and characterization.
(b) Determination of the atomic structures by X-ray crystallography.
(c) Dynamical properties study by high-speed AFM and MD simulations.
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| Outline of Final Research Achievements |
We fused the amylogenic peptides such as Amyloid beta (1-42) and Alpha-synuclein (61-95) at the C-terminal of the ferritin cage and thus, encapsulated a precise number of foreign peptides in vivo into the cage. Analytic assays like ThT and FT-IR confirmed the presence of beta-sheet structure inside the cage. We used high-speed AFM to visualize the encapsulated peptide oligomers by disassembling the ferritin cage at pH2.0. We observed that the amyloid core was surrounded by the ferritin subunits. The amyloid core showed dynamic behavior which changing the globular shape to linear over time. Unlike amyloid beta peptide, the alpha-synuclein oligomer dissociates with time. Overall, our studies demonstrated the precise encapsulation of amylogenic peptides into a restricted space which usually difficult to study in solution.
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| Academic Significance and Societal Importance of the Research Achievements |
Since the role of amylogenic peptides in brain disease is not clear yet, our current study is expected to be a useful from the view point of oligomer specific drug discovery because our system can isolate a precise oligomer and study the dynamic behavior of the oligomer in a confined environment.
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