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  • 标题:Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
  • 本地全文:下载
  • 作者:Milsee Mol ; Dipali Kosey ; Ramanamurthy Boppana
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2018
  • 卷号:8
  • 期号:1
  • 页码:3464
  • DOI:10.1038/s41598-018-21840-w
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:With the advent of synthetic biology in medicine many synthetic or engineered proteins have made their way to therapeutics and diagnostics. In this paper, the downstream gene network of CD14-TNF-EGFR pathway in leishmaniasis, a tropical disease, is reconstructed. Network analysis showed that NFkB links the signaling and gene network, used as a point of intervention through a synthetic circuit embedded within the negative autoregulatory feedback loop. A chimeric protein kinase C (PKC) is incorporated in the synthetic circuit, under the transcriptional regulation of Lac repressor and IPTG, as an inducer. The chimeric PKC_ζα via IκKb phosphorylation activates NFκB, and modulates the gene expression from an anti-inflammatory to a pro-inflammatory phenotype in in vitro L. major infected macrophage model. This is the first ever report of a synthetic device construction in leishmania.
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