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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences health sciences infectious diseases malaria
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences genetics epigenetics
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2016
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75724 Paris
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.