2015 Fiscal Year Research-status Report
喫煙によって引き起こされる慢性炎症の発症メカニズムの解明
| Project/Area Number |
25430182
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| Research Institution | Osaka University |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | Systems biology / Bioinformatics / Regulatory network / Immune system |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
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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| Strategy for Future Research Activity |
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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| Causes of Carryover |
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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| Expenditure Plan for Carryover Budget |
The money will be used for gene expression (RNA-seq) and transcription factor binding (ATAC-seq) measurements.
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