| 研究課題/領域番号 |
25430182
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| 研究機関 | 大阪大学 |
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研究代表者 |
ディエス ディエゴ 大阪大学, 免疫学フロンティア研究センター, 准教授 (90597741)
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| 研究分担者 |
熊谷 雄太郎 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00528408)
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| 研究期間 (年度) |
2013-04-01 – 2017-03-31
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| キーワード | Systems biology / Bioinformatics / Regulatory network / Immune system |
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| 研究実績の概要 |
1. Introduction: Respiratory disease like Chronic Obstructive Pulmonary Disease (COPD) and Silicosis are characterized by irreversible inflammation and disease progression, with important impact in health since COPD is one of the leading causes of death worldwide. The goal of this project is to understand the mechanisms leading to irreversible inflammation.
2. Methods: We integrate experimental data from a silicosis model with systems biology approaches. We measure changes in the expression of genes over time, and at different levels of silica exposure. We also measure the binding of transcription factors that regulate the expression of genes. We integrate this information with protein interactions, evolutionary conservation and other prior information to reconstruct the gene regulatory networks associated with the onset of irreversible inflammation.
3. We have successfully implemented the assay and bioinformatics methods necessary to detect transcription factor binding location. These methods will be necessary to reconstruct regulatory networks when the complete dataset is obtained.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
The initial study was planed on a mouse model of tobacco smoking, but because of difficulties implementing the model it had to be changed to a model of silicosis, delaying the overall start of the project. In addition, some of the samples are obtained one year after exposure to silica. Therefore, the schedule for this projects is somewhat shifted from the original plan.
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| 今後の研究の推進方策 |
Some samples will be collected after 1 year of the time of exposure to silica. To avoid biases introduced by batch effects all samples will be combined and expression and transcription factor measurements will be performed simultaneously. The data collected from these experiments will be analyzed with bioinformatics methods to determine the regulatory networks associated with irreversible inflammation.
The bioinformatics methods will be tested first on public datasets that collect both RNA-seq (gene expression) and ATAC-seq (transcription factor profiling). This will allows us to understand the limitations of the bioinformatics methods, and optimize the parameters for the reliable reconstruction of gene regulatory networks.
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| 次年度使用額が生じた理由 |
Although some of the samples have been collected (for mouse exposed to silica for 1 and 3 months), it is important to not analyze those samples first, and wait until all samples are available in order to minimize the effect of confounding variables like batch effects. Therefore, the money that was expected to be used for the expression and transcription factor binding experiments has not been used yet, as we need to wait until all the samples have been collected to perform those experiments.
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| 次年度使用額の使用計画 |
The money will be used for gene expression (RNA-seq) and transcription factor binding (ATAC-seq) measurements.
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