| Project/Area Number |
17K19204
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
Mori Takeshi 九州大学, 工学研究院, 准教授 (70335785)
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| Research Collaborator |
Tsukiji Shinya
Kawano Ryuji
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 膜貫通タンパク質 / シグナル伝達 / がん免疫療法 / 膜間貫通タンパク質 / キメラ型受容体 / ナノバイオ / バイオテクノロジー |
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| Outline of Final Research Achievements |
In this study, we aimed to develop transmembrane molecules and induce signal transduction. In the future, it may be a technology to modify immune cells for cancer immunotherapy. The following was clarified. 1. We established a high yield synthesis method of transmembrane molecules by click reaction. 2. An evaluation system for membrane permeation using a bilayer membrane was constructed, and it was shown that transmembrane molecules permeate through the membrane regardless of the presence or absence of the membrane potential. 3. Indirect and direct modification methods showed that the transmembrane molecules reacted with streptavidin remained on the cell membrane. However, no translocation of eDHFR-GFP, which was designed as a signal transduction model, to the cell membrane was observed. This indicates that there is a need to improve the molecular design of the transmembrane domain.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、遺伝子組み換えを行うことなく、外部から膜貫通分子を添加することで、膜タンパク質様の構造を作ることを目的とした。遺伝子組み換えによる細胞改変は、遺伝子変異のリスクがあり、細胞治療が高コストとなる原因であるため、これを解決できれば、大きなインパクトを与えうる。難易度の高いこの挑戦に対して、本研究により、膜貫通分子の高収率な合成法の確立、膜透過の証明を行うことができた。しかしながら、膜貫通状態にあると思われる分子が、細胞内タンパク質と結合せず、膜貫通領域の分子設計をより長くしたり、剛直にするなどの改善が必要であるという知見が得られた。
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