| Project/Area Number |
21K06029
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 43010:Molecular biology-related
|
|---|
| Research Institution | Institute of Physical and Chemical Research |
|---|
Principal Investigator |
DE HOON Michiel 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (70525617)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
蓑田 亜希子 国立研究開発法人理化学研究所, 生命医科学研究センター, 客員主管研究員 (40721569)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | electron microscopy / tomography / 3D genomics / promoters / enhancers / gene regulation / 3D reconstruction / histone modifications / in-situ hybridization / Tomography / Electron microscope / Chromatin structure / In-situ hybridization / Non-coding RNA / XIST / Chromatin 3D structure / Chromatin conformation / Electron microscopy / THP-1 Differentiation / Imaging / Hi-C |
|---|
| Outline of Research at the Start |
Physical interactions between genes and genomic control regions underlie gene regulation that determines cell type and cell state. We use electron microscopy to visualize those interactions at specific control regions at nanometer-scale resolution to understand the mechanism of gene regulation.
|
| Outline of Final Research Achievements |
How the genome functions physically remains to a large extent unknown. In this project, we used electron microscopy to image the genome and observe its machinery. While electron microscopy has a very high resolution allowing imaging of small details, it requires staining or labeling with metal to make important biomolecules visible in EM.
We developed methods to label regulatory biomolecules with metal beads, and stained DNA. As the final step in this project, we will take EM images of these samples from different angles, reconstruct a 3D model of gene regulation from these images, and identify the labeled biomolecules in the images.
|
| Academic Significance and Societal Importance of the Research Achievements |
The physical mechanisms by which genetic variants contribute to disease remain unclear. 3D imaging of the cell nucleus shows where important biomolecules are physically located relative to each other. Visualizing the genomic machinery helps to unravel the biophyical mechanisms underlying disease.
|
