Objective
The deadliest form of human malaria is caused by the protozoan parasite, Plasmodium falciparum, which annually infects millions worldwide. The virulence of P. falciparum is attributed to its ability to evade the human immune system, by modifying the host red blood cell surface to adhere to the vascular endothelium and to undergo antigenic variation. The main cell surface ligands responsible for both cytoadherence and antigenic variation are members of the P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1) family. These polymorphic proteins are encoded by a multi-copy gene family called var. Each individual parasite expresses a single var gene at a time, whereas the remaining ~60 var genes found in its genome are maintained in a transcriptionally silent state. Switches in PfEMP1 expression allow the parasite to avoid the human immune response and maintain a long-term infection. The regulation of var gene expression is therefore responsible for both immune evasion and the pathogenicity of the disease. Mutually exclusive expression and antigenic switching of var genes is epigenetically regulated at the level of transcription. This was recently demonstrated to involve chromatin modification, subnuclear localization, promoter/promoter interactions, and sterile RNAs. However, our understanding of the molecular mechanisms by which var genes are regulated is still elusive, particularly the aspects of var gene activation. I hypothesize that there exists a specific subnuclear var expression site that is involved in var gene activation. To this end the goals of the proposed research are: 1) to determine the capacity of the postulated var expression site and its role in var gene expression; 2) to determine the specificity of the expression site as a limiting factor for var gene regulation. This knowledge could lead to ways of disrupting the parasite’s ability to evade immune attack and could be exploited for the discovery of novel targets for drug and vaccine development.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences health sciences infectious diseases malaria
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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.
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.
FP7-PEOPLE-2007-4-3-IRG
See other projects for this call
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.
Coordinator
91904 JERUSALEM
Israel
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.