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

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 tha...

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Autores principales:	Milsee Mol, Dipali Kosey, Ramanamurthy Boppana, Shailza Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54af9ca372fc42489f10ae98202ac90a
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spelling	oai:doaj.org-article:54af9ca372fc42489f10ae98202ac90a2021-12-02T11:40:54ZTranscription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis10.1038/s41598-018-21840-w2045-2322https://doaj.org/article/54af9ca372fc42489f10ae98202ac90a2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21840-whttps://doaj.org/toc/2045-2322Abstract 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.Milsee MolDipali KoseyRamanamurthy BoppanaShailza SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Milsee Mol Dipali Kosey Ramanamurthy Boppana Shailza Singh Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
description	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.
format	article
author	Milsee Mol Dipali Kosey Ramanamurthy Boppana Shailza Singh
author_facet	Milsee Mol Dipali Kosey Ramanamurthy Boppana Shailza Singh
author_sort	Milsee Mol
title	Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
title_short	Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
title_full	Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
title_fullStr	Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
title_full_unstemmed	Transcription Factor Target Gene Network governs the Logical Abstraction Analysis of the Synthetic Circuit in Leishmaniasis
title_sort	transcription factor target gene network governs the logical abstraction analysis of the synthetic circuit in leishmaniasis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/54af9ca372fc42489f10ae98202ac90a
work_keys_str_mv	AT milseemol transcriptionfactortargetgenenetworkgovernsthelogicalabstractionanalysisofthesyntheticcircuitinleishmaniasis AT dipalikosey transcriptionfactortargetgenenetworkgovernsthelogicalabstractionanalysisofthesyntheticcircuitinleishmaniasis AT ramanamurthyboppana transcriptionfactortargetgenenetworkgovernsthelogicalabstractionanalysisofthesyntheticcircuitinleishmaniasis AT shailzasingh transcriptionfactortargetgenenetworkgovernsthelogicalabstractionanalysisofthesyntheticcircuitinleishmaniasis
_version_	1718395516430057472

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

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