Objective
Plasmodium parasites are the causative agents of malaria, amongst the most prevalent and severe human infectious diseases. Plasmodium sporozoites are injected into the mammalian host during the bite of an anopheline mosquito, and rapidly migrate to the liver where they invade hepatocytes. Once inside a hepatocyte, a single sporozoite initiates a developmental program whereby it gives rise to thousands of merozoites, which are released into the blood stream a few days later, initiating the clinical phase of malaria infection. Sporozoites are capable of entering any cell type tested thus far in vitro, and can even initiate transformation into exo-erythrocytic forms extracellularly, but can only undergo schizogony and generate infectious merozoites in a particular environment, which appears to be provided exclusively by hepatocytes and hepatoma cell lines. This strongly suggests a crucial role of the host cell in providing a distinct niche that supports Plasmodium growth and development. One distinctive feature of hepatocytes when compared to other epithelial cells is their mode of polarization. The general importance of host cell polarity for a liver stage Plasmodium infection has not been investigated. I propose to analyze the role of one unique aspect of hepatocyte biology, the hepatic mode of polarization, in creating the hepatocyte niche that uniquely supports liver stage Plasmodium growth and development. I will address this question by taking a broad approach to characterize the stages of Plasmodium development in WIF-B cells, which display hepatic polarity and to characterize the polarization state of Huh-7 cells, a hepatoma line widely used to assess infection. In a complementary candidate molecule approach, I will characterize the requirement for the host EMK1 kinase, which has a known role in generating hepatic polarity, and the siRNA mediated knockdown of which has a reproducible effect on Plasmodium infection.
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 cell biology cell polarity
- 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.
FP7-PEOPLE-2007-2-1-IEF
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
1649 028 Lisboa
Portugal
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.