Objective
During malaria transmission Plasmodium sporozoites actively enter the liver and transform into clinically silent liver stages (LS). Each individual LS undergoes multiple rounds of nuclear divisions and eventually produces thousands of first-generation merozoites that initiate the erythrocytic cycle causing malaria pathology.
Liver stages are ideal targets for causal prophylactic drugs and vaccine strategies. Immunization with radiation- or genetically-attenuated parasites confers protective immunity against live sporozoite challenge. This protection relies primarily on CD8+ T cell responses against parasite antigens expressed by early LS, but the nature of these antigens still remains unknown.
Recent advances in the identification of Plasmodium genes which a re specifically expressed during LS development opened new opportunities to study these stages. Here, I propose to employ a reverse genetic approach to identify parasite genes that perform essential functions during LS development. Using gene targeting in the Plasmodium berghei rodent malaria model, I will produce parasite knockout mutants for genes specifically expressed throughout LS development.
Importantly, I expect to generate attenuated parasites blocked at different stages (early, intermediate, and l ate) during LS development. I will include gene products with potential roles in selective protein processing and degradation, since they may constitute potential targets for causal prophylactic anti-malarial drugs. Mutants that attenuate during LS development will be tested for their ability to induce protective immune responses in mice.
Ultimately, the characterization of the antigenic repertoire of protective versus non-protective mutants will help defining parasite gene products specifically associated with protection against Plasmodium liver stages. This fellowship will provide me with an excellent training in reverse genetics, and will be critical for the continuation of my career as a researcher.
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 basic medicine immunology immunisation
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences basic medicine pathology
- natural sciences biological sciences zoology invertebrate zoology
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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.
FP6-2005-MOBILITY-5
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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
HEIDELBERG
Germany
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.