Project description
Understanding malaria parasite fate decisions in the liver
Despite significant efforts to eradicate malaria, our limited understanding of the Plasmodium parasite and its interactions with hosts continues to hamper progress. Recent research has uncovered new insights into the parasite’s life cycle, including dormant and sexually committed forms in the liver, but the mechanisms driving these developmental choices remain unclear. Using engineered human microlivers, humanised mouse models, trans-species studies, and single-cell technologies, the ERC-funded DEXES project will explore the molecular mechanisms involved in dormancy, activation, and sexual conversion. It will also examine how host and parasite cell-fate interactions influence treatment outcomes.
Objective
Malaria remains a devastating public health burden the estimated death toll in 2020 was over 600,000. Its eradication is a desirable goal; however, the development of novel intervention strategies is hampered by limited current understanding of the biology of Plasmodium, the causative agent of malaria, and of its complex interactions with mammalian and mosquito hosts. In the liver, inside hepatocytes, Plasmodium parasites can either 1) replicate, forming new parasites that will infect erythrocytes and cause disease, or 2) remain dormant, which can lead to chronic, relapsing disease weeks to years after the original infection. I recently discovered new hepatic outcomes using a novel pipeline for single-cell hepatocyte-pathogen sequencing. I have identified sub-populations of sexually committed parasite forms, previously thought to appear only during erythrocytic infection. This groundbreaking insight into the Plasmodium life cycle can change our understanding of malaria transmission, yet it remains unknown how malaria parasites commit to these different developmental outcomes in hepatocytes.
DEXES will test the hypothesis that Plasmodium liver infection outcomes depend upon the metabolic state of the host hepatocyte. Using engineered human microlivers, new humanized mouse models, trans-species studies and single-cell technologies, I will: 1) identify parasite-encoded molecular mechanisms implicated in the induction and maintenance of dormancy, activation, and sexual conversion in the liver, and 2) establish the bidirectional relationships between host metabolism and distinct parasite cell fates and their impact on treatment outcomes.
This project will uncover the molecular mechanisms underpinning dormancy, relapsing and transmission of malaria parasites, and lay the groundwork for the future development of new therapies targeting the liver infection reservoirs.
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
- engineering and technology other engineering and technologies microtechnology organ on a chip
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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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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.
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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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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-COG
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75654 PARIS
France
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