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REACT SIGNED

Uncovering the role of cis genetic elements in antigenic variation of Plasmodium falciparum using the CRISPR-Cas9 genome editing technology

Total Cost €

0

EC-Contrib. €

0

Partnership

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 REACT project word cloud

Explore the words cloud of the REACT project. It provides you a very rough idea of what is the project "REACT" about.

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Project "REACT" data sheet

The following table provides information about the project.

Coordinator
INSTITUT PASTEUR 

Organization address
address: RUE DU DOCTEUR ROUX 25-28
city: PARIS CEDEX 15
postcode: 75724
website: http://www.pasteur.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 185˙076 €
 EC max contribution 185˙076 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-01-01   to  2020-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT PASTEUR FR (PARIS CEDEX 15) coordinator 185˙076.00

Map

 Project objective

Malaria is an infectious human disease caused by parasitic protozoans of the Plasmodium type. P. falciparum causes the most lethal form with about 400.000 deaths annually. Pathogenesis involves expression of clonally variant molecules encoded by multi gene families at the surface of the infected host cells (erythrocyte). The most important virulence factor is called PfEMP1, which undergoes antigenic variation and is encoded by 60 var gene members. Despite the major scientific efforts, the molecular mechanisms orchestrating antigenic variation are still elusive. The reason is the lack of tools to perform genome editing in the natural epigenetic context, which is crucial in this important immune escape process. We aim to investigate antigenic variation of P. falciparum, by means of the recently developed CRISPR-Cas9 tool. This genome editing technology allows the in situ genetic manipulation of var gene regulatory elements in a native chromatin context. Virtually, any locus can be targeted by a RNA guide to insert, exchange or delete specific DNA regions including generation of point mutations without introducing a selective marker. Alternatively, we will use a dead Cas9 version (dCas9), which consist on the targeting of the desired locus by an inactive Cas9. This dCas9 can be fused to protein tags or effectors. We will use these techniques to i) delete cis-regulatory elements of var genes, ii) to identify factors associated to cis-regulatory elements by Cas9 targeted immunoprecipitations and iii) to engineer a tool to perform activation/silencing of specific var genes by fusing the dCas9 with epigenetic effector molecules (silencing and activators). This project will combine state-of-the-art techniques in genome editing to study malaria parasite virulence and provide reliable, accurate and focused data about the implication of epigenetics in the process of antigenic variation. The new tools developed in this project will be highly relevant for other human pathogens.

 Publications

year authors and title journal last update
List of publications.
2020 Anna Barcons-Simon, Carlos Cordon-Obras, Julien Guizetti, Jessica M. Bryant, Artur Scherf
CRISPR Interference of a Clonally Variant GC-Rich Noncoding RNA Family Leads to General Repression of var Genes in Plasmodium falciparum
published pages: , ISSN: 2150-7511, DOI: 10.1128/mbio.03054-19
mBio 11/1 2020-04-01

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