Project description
Understanding Plasmodium parasites for antimalarial strategies
Plasmodium parasites, the cause of malaria, rely on unique proteins for sexual replication in mosquitoes, yet their development is not fully understood. A recently discovered actin-related protein 2/3 (Arp2/3) complex plays a crucial role in DNA segregation and oocyst development, but its activation mechanisms are still unclear. The ERC-funded PlasmoArp project will investigate the activation of the Plasmodium Arp2/3 complex during gamete formation and its unique regulatory mechanisms. It will explore the connection between Arp2/3 and a previously unknown spindle assembly checkpoint regulating mitosis. The project will also examine why Arp2/3-deficient parasites arrest in oocysts, shedding light on the cell division processes. PlasmoArp will make use of molecular biology techniques, single-cell transcriptomics and advanced imaging and develop a new genetic tool for dissecting oocyst-specific gene function.
Objective
The malaria-causing Plasmodium parasites often use highly divergent proteins to regulate fundamental biological processes, such as sexual replication in the mosquito. Therefore, the molecular and cellular biology underlying parasite development is often little understood, especially during the mosquito stages, a major bottleneck in the Plasmodium life cycle. Recently, I identified an unconventional, Plasmodium-specific actin-related protein 2/3 (Arp2/3) complex that mediates DNA segregation during male gamete formation and is essential for development of the main replicative mosquito stage, the oocyst. Understanding the regulation and function of this structurally and functionally divergent actin nucleator could provide targets for new antimalarial strategies. Here, I propose to elucidate the molecular mechanism of the Plasmodium Arp2/3 complex on three levels: (1) I will uncover how Arp2/3 is activated during gamete formation, revealing the likely unusual mode of regulation of this complex. (2) I will explore the hypothesis that Arp2/3 is linked to a cryptic spindle assembly checkpoint, a mitosis regulator so far thought to be absent in Plasmodium. (3) I will reveal why Arp2/3-deficient parasites arrest in oocysts, which will shed light on the unusual cell division mode of this elusive stage. To address these ambitious aims, I will combine molecular biology methods, single cell transcriptomics and imaging, and I will engineer a new genetic tool to dissect gene function specifically in the oocyst, a stage that is notoriously difficult to study. PlasmoArp will thus not only give insight into the molecular biology of Plasmodium development in the mosquito and advance our understanding of Arp2/3 and actin biology across the eukaryotic kingdom, but it will also expand the toolbox to study the neglected oocyst. As Plasmodium Arp2/3 is essential for malaria transmission, this research will pave the way for new intervention strategies to mitigate malaria infections.
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 biochemistry biomolecules proteins
- 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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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-2024-STG
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69120 Heidelberg
Germany
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