National Centre for Cell Science, NCCS Complex, Ganeshkhind, SP Pune University Campus, Pune, 411007, India.
Sci Rep. 2018 Feb 22;8(1):3464. doi: 10.1038/s41598-018-21840-w.
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.
随着医学中合成生物学的出现,许多合成或工程蛋白已经应用于治疗和诊断。在本文中,我们重建了热带疾病利什曼病中 CD14-TNF-EGFR 途径的下游基因网络。网络分析表明,NFkB 连接信号和基因网络,可作为通过嵌入负反馈回路中的合成电路进行干预的切入点。在 Lac 阻遏物和 IPTG 的转录调控下,将嵌合蛋白激酶 C(PKC)整合到合成电路中作为诱导剂。嵌合 PKC_ζα 通过 IκKb 磷酸化激活 NFκB,并调节体外 L. major 感染的巨噬细胞模型中从抗炎到促炎表型的基因表达。这是在利什曼原虫中构建合成装置的首例报道。