Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis

Scientific Reports
Milsee MolShailza Singh

Abstract

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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Citations

May 18, 2021·Frontiers in Cellular and Infection Microbiology·Elvira Cynthia Alves HorácioLaila Alves Nahum

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Methods Mentioned

BETA
nuclear translocation
NMR
transfection
transgenic
RNA-seq
X-ray
confocal microscopy
PCR

Software Mentioned

- Web
[UNK] Real - Time PCR System
R
BLASTp
Bioconductor
Berkeley Madonna
BoolNet
ImageJ2
ProSA
GRENITS

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