Project description
Cell cycle progression model to combat malaria
Plasmodium falciparum, the deadliest malaria parasite, multiplies in red blood cells by producing tens of thousands of daughter cells in a single cycle, demonstrating a unique cell cycle architecture. The ERC-funded Janus project will focus on an essential process for parasite survival, potentially offering new insights to combat malaria. It will investigate how a transcriptional clock regulates the cell cycle while local players modulate the activity of effectors through phosphorylation. The project will use single-cell transcriptomics and high-resolution phospho-proteomics to explore how these mechanisms connect to cell cycle events. It will investigate their roles in normal progression and controlled arrest, identify cell cycle regulators, and integrate the data to develop a comprehensive model of cell cycle progression.
Objective
All eukaryotic cell multiplication requires well-orchestrated developmental programs and regulatory pathways to guarantee fidelity in transmission of genetic information. Multiplication inside red blood cells of Plasmodium falciparum, the deadliest malaria parasite, is responsible for malaria pathogenicity. Unlike model organisms, Plasmodium divides in unconventional ways producing not two but up to tens of thousands of daughter cells, in a single cell cycle round. This points to a yet-to-be-explored original and divergent cell cycle architecture where conventional rules likely do not apply.
We hypothesise that a transcriptional clock paces the cell cycle while a network of local players modulates and fine-tunes the activity of effectors through phosphorylation. To test this hypothesis, we will first use single cell transcriptomics and high resolution phospho-proteomics to understand how these are connected with cell cycle events and their contribution to normal progression and controlled cell cycle arrest. Secondly, we will conduct a genome-scale conditional genetic screen to identify cell cycle regulators we will map progression of pooled barcoded mutants using cell cycle reporters, barseq and single cell transcriptomic readouts. Finally, we will combine the data collected throughout the JANUS project and provide an integrated model of cell cycle progression, checkpoints, their associated transcriptional and signalling events, and their interdependence. Furthermore, we will functionally dissect on a gene-by-gene basis the entrance into the replicative phase based on our modelled data.
Altogether the JANUS project will provide insights into an ancient, yet divergent process, essential for parasite survival and propagation with unprecedented detail. It may reveal innovative eukaryotic adaptations to cell cycle control in this basal lineage which could generate new insights into protist biology and provide new tools in the continuing fight 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 cell biology cell signaling
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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
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.
(opens in new window) ERC-2023-STG
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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.
75794 PARIS
France
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