Project description
Molecular mechanisms in the lifecycle of the Plasmodium parasite
Despite research efforts over the years, malaria remains a major health issue. The complex biology of the Plasmodium parasite, transmitted by mosquitoes, poses challenges in developing new interventions. Plasmodium initially travels through the bloodstream and reaches the liver where it undergoes a period of growth and multiplication. Funded by the European Research Council, the PASSAGE project is interested in investigating the molecular mechanisms underlying the liver stage of the parasite life cycle. Researchers will build on recent evidence linking the liver stage with DNA damage, which likely causes genetic variability and may impact disease severity. Investigating these dynamics could yield crucial insights for combating malaria through targeted interventions.
Objective
A world free of malaria is certainly a desirable goal. However, in spite of the significant incidence reduction achieved globally between 2000-2015, malaria still kills a child every minute. The limited understanding of Plasmodiums biology hampers the development of novel intervention strategies. Upon transmission by Anopheles mosquitos, Plasmodium parasites must reach the liver and infect hepatocytes. Inside a hepatocyte, each parasite replicates into thousands of new erythrocyte-infectious forms, which lead to disease. The parasite biomass generated during the liver stage (LS) of infection is directly associated with malaria severity, but how the parasite achieves such a high replication rate, and the consequences of that, remain utterly unexplored. Notably, Plasmodium replication is unusual. The parasite divides by schizogony, with divisions occurring without cytokinesis and it cannot salvage pyrimidines from the environment, relying solely on nucleotides synthesized de novo. Using a Plasmodium transgenic line specifically designed to study DNA replication throughout parasite development, I unveiled for the first time the temporal dynamics of DNA replication throughout parasite LS and show that Plasmodiums LS high replication rate is accompanied by DNA damage. Thus, I hypothesize that DNA damage accumulation during LS schizogony is a generator of genetic variability prior to intra-erythrocytic infection. By using a combination of molecular, cell biology and genetic approaches, I now propose to characterize the mechanisms, define the molecular players, and reveal the causes and consequences of such a high replication rate in the outcome of infection and progression of disease, by exposing the consequences for parasite genetic diversity and virulence. Connecting LS schizogony with parasite genetic diversity and virulence for the first time will be conceptually transformative, and will certainly provide valuable targets and tools for the combat against malaria.
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 biological sciences genetics DNA
- natural sciences biological sciences genetics nucleotides
- agricultural sciences agricultural biotechnology biomass
- 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.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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
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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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-ADG
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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.
1649-035 LISBOA
Portugal
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