| 研究課題/領域番号 |
23K21316
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| 補助金の研究課題番号 |
21H02496 (2021-2023)
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| 研究種目 |
基盤研究(B)
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| 配分区分 | 基金 (2024)
補助金 (2021-2023) |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分44020:発生生物学関連
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
Moore Adrian 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (30442932)
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| 研究期間 (年度) |
2021-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2024年度)
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| 配分額 *注記 |
17,160千円 (直接経費: 13,200千円、間接経費: 3,960千円)
2024年度: 4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2023年度: 4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2022年度: 4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2021年度: 4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
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| キーワード | Dendrite / Microtubule nucleation / microtubule / neurons / differentiation / regeneration / neuron / dendrite / axon / neurom / software / differentitaion / neuron differentiation / neuron regeneration |
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| 研究開始時の研究の概要 |
We expect that Pfn4 is present at the local center where microtubules are generated during dendrite arbor differentiation. It amplifies microtubule generation at these sites. We plan to investigate the localization of Pfn4 in the developing dendrite arbor. We will use in vivo imaging and develop new machine learning-based computer vision techniques to link the appearance of final arbor wiring features to the output of earlier local cytoskeletal organization events.
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| 研究実績の概要 |
We are defining the cellular and molecular nature of microtubule generation mechanisms in neurons. Then, we will examine the functional significance of these mechanisms in arbor differentiation, connectivity, and plasticity. Disrupted microtubule regulation occurs in many neurological diseases, and new microtubule growth promotes neuron regeneration. Discovering specialized neuronal mechanisms for microtubule generation is one approach to providing unique drug targets for manipulating neuron differentiation and regeneration.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
We have examined Sonorin localization in the developing dendrite arbor. We examined the function of Sonorin in local control of microtubule generation using the same approaches as our previous studies. We have developed in vivo imaging with machine learning-based computer vision techniques to link the appearance of final arbor wiring features to the output of earlier local cytoskeletal organization events. We use synthetic images that mimic our imaging parameters to replace limited traditional manually annotated training datasets. This new approach dramatically advances our ability to segment our imaging data automatically. These new tools will make long-term, multi-measurement quantitative sequencing of live arbor differentiation a new standard for the field.
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| 今後の研究の推進方策 |
We will use in vivo time-lapse tracking and EB1::GFP comet tracks, which bind the continuously expanding and retracting MT plus ends. Furthermore, MT nucleation plays a pivotal role in modulating post-injury neuron protection and regeneration. After neuron injury, MT nucleation activity significantly increases to promote the production of dynamic MTs throughout the neuron, this increase in dynamic MTs assists the injured neuron against injury-induced degradation and promotes neuron regeneration. Does Sonorin-mediated MT generation play a part in this process? I will investigate the function of Sonorin in a cellular context by inducing neuron damage to trigger a rapid upregulation of MT generation in the post-mitotic neurons and examine its role in injury-induced degeneration protection.
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