An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum

Abstract Establishing robust genome engineering methods in the malarial parasite, Plasmodium falciparum, has the potential to substantially improve the efficiency with which we gain understanding of this pathogen’s biology to propel treatment and elimination efforts. Methods for manipulating gene ex...

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Autores principales:	Armiyaw S. Nasamu, Alejandra Falla, Charisse Flerida A. Pasaje, Bridget A. Wall, Jeffrey C. Wagner, Suresh M. Ganesan, Stephen J. Goldfless, Jacquin C. Niles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9d76cd561ad4d1a993ae54780056e38
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spelling	oai:doaj.org-article:e9d76cd561ad4d1a993ae54780056e382021-12-02T15:23:06ZAn integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum10.1038/s41598-020-77644-42045-2322https://doaj.org/article/e9d76cd561ad4d1a993ae54780056e382021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77644-4https://doaj.org/toc/2045-2322Abstract Establishing robust genome engineering methods in the malarial parasite, Plasmodium falciparum, has the potential to substantially improve the efficiency with which we gain understanding of this pathogen’s biology to propel treatment and elimination efforts. Methods for manipulating gene expression and engineering the P. falciparum genome have been validated. However, a significant barrier to fully leveraging these advances is the difficulty associated with assembling the extremely high AT content DNA constructs required for modifying the P. falciparum genome. These are frequently unstable in commonly-used circular plasmids. We address this bottleneck by devising a DNA assembly framework leveraging the improved reliability with which large AT-rich regions can be efficiently manipulated in linear plasmids. This framework integrates several key functional genetics outcomes via CRISPR/Cas9 and other methods from a common, validated framework. Overall, this molecular toolkit enables P. falciparum genetics broadly and facilitates deeper interrogation of parasite genes involved in diverse biological processes.Armiyaw S. NasamuAlejandra FallaCharisse Flerida A. PasajeBridget A. WallJeffrey C. WagnerSuresh M. GanesanStephen J. GoldflessJacquin C. NilesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Armiyaw S. Nasamu Alejandra Falla Charisse Flerida A. Pasaje Bridget A. Wall Jeffrey C. Wagner Suresh M. Ganesan Stephen J. Goldfless Jacquin C. Niles An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum
description	Abstract Establishing robust genome engineering methods in the malarial parasite, Plasmodium falciparum, has the potential to substantially improve the efficiency with which we gain understanding of this pathogen’s biology to propel treatment and elimination efforts. Methods for manipulating gene expression and engineering the P. falciparum genome have been validated. However, a significant barrier to fully leveraging these advances is the difficulty associated with assembling the extremely high AT content DNA constructs required for modifying the P. falciparum genome. These are frequently unstable in commonly-used circular plasmids. We address this bottleneck by devising a DNA assembly framework leveraging the improved reliability with which large AT-rich regions can be efficiently manipulated in linear plasmids. This framework integrates several key functional genetics outcomes via CRISPR/Cas9 and other methods from a common, validated framework. Overall, this molecular toolkit enables P. falciparum genetics broadly and facilitates deeper interrogation of parasite genes involved in diverse biological processes.
format	article
author	Armiyaw S. Nasamu Alejandra Falla Charisse Flerida A. Pasaje Bridget A. Wall Jeffrey C. Wagner Suresh M. Ganesan Stephen J. Goldfless Jacquin C. Niles
author_facet	Armiyaw S. Nasamu Alejandra Falla Charisse Flerida A. Pasaje Bridget A. Wall Jeffrey C. Wagner Suresh M. Ganesan Stephen J. Goldfless Jacquin C. Niles
author_sort	Armiyaw S. Nasamu
title	An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum
title_short	An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum
title_full	An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum
title_fullStr	An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum
title_full_unstemmed	An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum
title_sort	integrated platform for genome engineering and gene expression perturbation in plasmodium falciparum
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e9d76cd561ad4d1a993ae54780056e38
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An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum

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