Development of virus-based vector for local translatino in neuron to analyze high-order brain function
| Project/Area Number |
19K22353
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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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| Review Section |
Medium-sized Section 42:Veterinary medical science, animal science, and related fields
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| Research Institution | Nagasaki University |
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Principal Investigator |
YOSHII Kentaro 長崎大学, 感染症共同研究拠点, 教授 (50421988)
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| Project Period (FY) |
2019-06-28 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 局所翻訳 / フラビウイルス / ウイルスベクター / 脳の高次機能 / 神経変性疾患 |
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| Outline of Research at the Start |
神経細胞は 局所翻訳と呼ばれる、mRNAの神経突起内輸送・翻訳を行っており、脳の高次機能を制御すると考えられているが、その機序は殆ど不明である。本研究では、ウイルスRNAによる局所翻訳利用に着目し、解析することでウイルスエレメントを利用した局所翻訳特異的な発現ベクターを構築し、局所翻訳が関与する脳の高次機能の全容解明のための基盤情報を得る
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| Outline of Final Research Achievements |
It has been reported that mRNAs are transported and locally translated in neuronal dendrites. Transport of the mRNA and local translation in neuronal dendrites have been shown to be important for neurogenesis and the plasticity of the synaptic communication. Furthermore, disruption of the neuronal granule system has been shown to be involved in mental retardation and neurodegenerative diseases. In this study, we focused on a neuro-tropic flavivirus which uses the mRNA transport mechanism for the viral RNA transport in dendrites, and tried to apply it to vector for local protein translation in neurons. We constructed a reported virus which expressed heterologous genes, and mice were infected with the virus. The heterologous gene was successfully expressed in the brain indicating that the virus can be applied for the development of the virus vector for local translation in dendrites of neurons.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで脳の高次機能における局所翻訳の重要性は指摘されていたものの、生体レベルで諸因子の機能を解析するには遺伝子改変動物の使用以外に方法は無く、解析が困難であった。本研究の成果を基盤として任意の局所翻訳因子の発現が可能になれば、これまで解析が困難であった諸因子の局所翻訳における詳細な機能解析が容易に行えるようになり、脳の高次機能制御に関わる重要な基盤情報収集が飛躍的に進むと期待される。
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Report
(4 results)
Research Products
(70 results)
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[Journal Article] A novel nairovirus associated with acute febrile illness in Hokkaido, Japan.2021
Author(s)
Kodama F, Yamaguchi H, Park E, Tatemoto K, Sashika M, Nakao R, Terauchi Y, Mizuma K, Orba Y, Kariwa H, Hagiwara K, Okazaki K, Goto A, Komagome R, Miyoshi M, Ito T, Yamano K, Yoshii K, Funaki C, Ishizuka M, Shigeno A, Itakura Y, Bell-Sakyi L, Edagawa S, Nagasaka A, Sakoda Y, Sawa H, Maeda K, Saijo M, Matsuno K
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Journal Title
Nat Commun
Volume: 12
Issue: 1
Pages: 5539-5539
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Detection of a novel tick-borne flavivirus and its serological surveillance.2019
Author(s)
Shimoda H, Hayasaka D, Yoshii K, Yokoyama M, Suzuki K, Kodera Y, Takeda T, Mizuno J, Noguchi K, Yonemitsu K, Minami S, Kuwata R, Takano A, Maeda K.
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Journal Title
Ticks Tick Borne Dis.
Volume: -
Issue: 4
Pages: 742-748
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] A novel tick-borne flavivirus discovered in Zambia is closely related to Ngoye virus, representing a distinct lineage within the genus Flavivirus.2019
Author(s)
Hayato Harima, Shiho Torii, Yongjin Qiu, Masahiro Kajihara, Yoshiki Eto, Yasuko Orba, Yuki Eshita, Barnard M Hang' ombe, Kentaro Yoshii, Martin Simuunza, Hirofumi Sawa.
Organizer
第67回日本ウイルス学会学術集会
Related Report
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