Objective
Plasmodium falciparum, the protozoan parasite responsible for the lethal form of human malaria, causes between 1 and 3 million deaths every year. Within erythrocytes, the malarial parasite is surrounded by a vacuole as a consequence; it is separated from t he extracellular environment by three different membranes. The intracellular survival of the parasite requires a bidirectional vesicular transport system, regulated by Rab GTPases. The aim of this project is to determine whether vesicular transport is regulated in parasites by phosphorylation of Rab GTPases by protein kinases.
This application is based in the post-genomic era, where the identification of novel drug targets is facilitated by the availability of parasite genome databases. It is functional genomics and combines genetics with cellular biology and biochemistry. Preliminary experiments have established that P. falciparum Rab11B can be phosphorylated in vitro by the P. falciparum PfPK7. We intend to extend this study to the 10 other parasite Rabs using the 13 protein kinases for which we have active recombinant enzymes.
The identification of the regulation network of this bidirectional vesicular transport is essential to understand the development of the parasite. Once we have determined which R abs are substrates for a given kinase we will confirm the interacting complex in vivo by combining Pull-Down experiments and Mass Spectrometry studies. Mass Spectrometry will also be used to identify the phosphorylated residues in each Rab and the site will be altered by mutagenesis.
The impact of phosphorylation on Rab-mediated vesicular transport will be assessed by knocking-in mutated P. berghei genes coding for phosphorylation-resistant Rab GTPases. Demonstration that phosphorylation can regulate bidirectional vesicular transport within infected erythrocytes will render these novel Rab-kinases ideal targets for the development of new anti-malarial drugs.
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
- natural sciences computer and information sciences databases
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
FP6-2004-MOBILITY-11
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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
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.