2021 Fiscal Year Research-status Report
Transposable elements shape the evolution of mammalian innate immunity against pathogens
| Project/Area Number |
21K15066
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| Research Institution | Kyoto University |
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Principal Investigator |
CHEN Xun 京都大学, 高等研究院, 特定助教 (30885158)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | Transposable element / Immune cells / Evolution / Macrophages |
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| Outline of Annual Research Achievements |
We have collected 3-4 healthy human, crab-eating macaque and mouse blood samples for the enrichment of macrophage or monocyte cells. Samples were mainly obtained from Dr. Ryo Yamamoto lab at Kyoto University.
We have analyzed publicly available RNA-seq data and identified 31 upregulated transposable elements (TEs) that were induced by bacterial infection. Briefly, we first downloaded RNA-seq data of macrophages derived from 61 individuals before and after listeria monocytogenes and salmonella infection. We also re-analyzed RNA-seq data of macrophages derived from 39 individuals before and after influenza virus infection. After the TE differential expression analysis, we successfully identified 31 TE families that were specially upregulated following bacterial infection.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
Based on our another work focusing on the transcriptional and epigenetic response upon influenza infection, we identified 204 families that were upregulated following infection. Thus, we hypothesized that some upregulated TE families may be pathogen-specific.
To address this question, we slightly adjusted our research aims to first answer the key question toward which TEs are associate to the bacterial or viral infection in human macrophages. Then, we could compare the upregulated TE families between species to dissect the roles that TEs play during the evolution of innate immunity against infection.
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| Strategy for Future Research Activity |
Firstly, we will follow our original plans to study the epigenetic changes in TEs between human, crab-eating macaque and mouse following bacterial and viral infection. Using our established analytical platform for TEs, we will study the transcription and epigenetic changes in TEs between species.
Secondly, we will also analyze the RNA-seq of human samples following various viral infection to confirm the TE families that are specifically upregulated by bacterial infection.
Thirdly, we will perform the motif analysis to predict Transcription factors (TFs) that are associated with the upregulated TE families to understand the molecular mechanism and biological function upon bacterial infection. We will also perform the Chip-Seq to validate the binding of predicted TFs to each TE family.
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| Causes of Carryover |
We will perform the infection experiment using the collected macrophages or monocytes in this facial year. After that, we will also generate the transcriptome and epigenetic data. Meanwhile, we will also perform the bioinformatic analysis of generated RNA-seq and ATAC-seq data.
We will further discuss our latest results at the 45th Annual Meeting of the Molecular Biology Society of Japan and the 2022 Annual Meeting of the American Society of Human Genetics.
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