| Project/Area Number |
20H00476
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 45:Biology at organismal to population levels and anthropology, and related fields
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| Research Institution | Okayama University |
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Principal Investigator |
ROBINSON ROBERT 岡山大学, 異分野基礎科学研究所, 客員教授 (60814118)
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| Co-Investigator(Kenkyū-buntansha) |
千住 洋介 岡山大学, 異分野基礎科学研究所, 研究准教授 (90536848)
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| Project Period (FY) |
2020-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥45,760,000 (Direct Cost: ¥35,200,000、Indirect Cost: ¥10,560,000)
Fiscal Year 2024: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
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| Keywords | Eukaryogenesis / Cytoskeleton / Asgard Archaea / Evolution / Roadblock proteins / Rab GTPases / Endoplasmic Reticulum / Sec61 / Actin / Asgard archaea / cytoskeleton / Tubulin / Small GTPases / Asgard / Structure / Gelsolin / evolution / archaea / structural biology / metagenomics |
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| Outline of Research at the Start |
The origin of the eukaryotic cell is controversial. Metagenomics sequencing has revealed that Asgard archaea genomes contain potential homologs to eukaryotic genes. We will structurally characterize the Asgard eukaryotic-like protein homologs using X-ray crystallography and cryo-electron microscopy.
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| Outline of Annual Research Achievements |
We have analyzed the structures of Asgard archaea small GTPases, roadblock proteins and TRAPP proteins. The GTPase structure is similar to Rab GTPases, which in eukaryotes control the trafficking of vesicles between internal membranes. Asgard archaea do not possess internal membranes. However, the Asgard Rabs do not possess the C-terminal modification sites, which are needed to locate to discrete eukaryotic membranes. Thus, Rab proteins evolved their membrane specificity after proto-eukaryotes separated from Asgard archaea. The roadblock and TRAPP structures are also very similar between eukaryotes and Asgard archaea. However, Asgard form homodimers, whereas eukaryotes form heterodimers, indicating gene duplication and diversification were an important processes for eukaryotic evolution.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Over the past year we have made several unexpected discoveries through expressing Asgard archaea proteins in mammalian cells. Several Asgard protein classes localize to the same regions of the eukaryotic cell as their eukaryotic counterparts. In particular, some proteins localize to eukaryotic internal membranes, which do not exist in Asgard archaea. These data have given us a new insight that the properties of existing pre-eukaryotic machines shaped the process of eukaryogenesis, since their fundamental properties remain intact during 2 billion years of evolution. This insight has advanced our understanding beyond what we proposed at the beginning of the project. Based on this understanding, we expect to make outstanding progress in the last year of our project.
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| Strategy for Future Research Activity |
We have achieved most of the aims listed in our proposal. In our final year we will: 1)Carry out mass spectrometry analysis of Asgard proteins against mammalian extracts to look for protein interactions that have been maintained over 2 billion years of evolution; 2) Conduct further structural and biochemical analyses of Asgard gelsolin proteins; 3) Carry out biochemical analyses of Asgard membrane remodeling proteins.
Challenges: One major challenge is that publication costs have increased dramatically during the lifetime of this grant.
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