In vitro translation and analysis of neurodegenerative diseases
| Project/Area Number |
17H04995
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
System genome science
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| Research Institution | University of Hyogo |
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Principal Investigator |
Machida Kodai 兵庫県立大学, 工学研究科, 准教授 (20553093)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Keywords | 再構成型タンパク質合成系 / 神経変性疾患 / 翻訳機構 / バイオテクノロジー / 生体分子 / 脳神経疾患 |
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| Outline of Final Research Achievements |
We succeeded in reproducing Repeat Associated Non-AUG translation, which is an irregular protein translation depends on CAG repeat sequences that cause human neurodegenerative diseases using a reconstituted protein synthesis system constructed with purified human translation factors. These results indicating that the translation reactions that cause neurodegenerative diseases occur if there is a translation-related factors such as mRNA, ribosome, translation initiation factors, translation elongation factors, and translation termination factors. This study established the technical basis for reproducing and analyzing the irregular translation mechanism that causes neurodegenerative diseases in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、神経変性疾患の原因となるタンパク質凝集、具体的にはポリグルタミン病を引き起こすCAGリピート配列からの翻訳と翻訳産物の凝集をヒト因子由来の試験管内翻訳系で再現・解析するための技術基盤を確立した。リポソーム化を取り入れ細胞サイズの反応系場での解析も行えるようにした。本実験系はヒトの翻訳関連因子のみで再構築したものであり、試験管内でヒトの疾患に関連する遺伝子の一連の翻訳反応について新たな知見を得ることができるようになったため学術的意義が大きい。また、ヒト因子由来の実験系であるため、得られたデータを直接的に治療法開発へ応用できる可能性が高いという利点もあり、社会的な意義も大きい。
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Report
(5 results)
Research Products
(30 results)
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[Journal Article] Distinct roles and actions of protein disulfide isomerase family enzymes in catalysis of nascent-chain disulfide bond formation2021
Author(s)
Hirayama, C., Machida, K., Noi, K., Murakawa, T., Okumura, M., Ogura, T., Imataka, H., and Inaba, K.*
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Journal Title
iScience
Volume: 4
Issue: 4
Pages: 102296-102296
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] HCV IRES captures an actively translating 80S ribosome2019
Author(s)
Yokoyama Takeshi、Machida Kodai、Iwasaki Wakana、Shigeta Tomoaki、Nishimoto Madoka、Takahashi Mari、Sakamoto Ayako、Yonemochi Mayumi、Harada Yoshie、Shigematsu Hideki、Shirouzu Mikako、Tadakuma Hisashi、Imataka Hiroaki、Ito Takuhiro
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Journal Title
Molecular Cell
Volume: 印刷中
Issue: 6
Pages: 1205-1214
DOI
Related Report
Peer Reviewed / Open Access
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