Project description
Solving the mystery of malaria dormancy
Malaria is a life-threatening disease caused by Plasmodium parasites, which are transmitted to humans through the bites of infected Anopheles mosquitoes. The parasites cause disease by infecting red blood cells but prior to that can exist in a dormant liver stage as hypnozoites. Hypnozoites can become reactivated and cause recurrent blood-stage infections without further mosquito bites. The ERC-funded Host4Hypnozoites project aims to shed light on the longstanding mystery of hypnozoite dormancy. Researchers will characterise the cellular environment that supports dormancy, explore reactivation kinetics within the host, and identify factors that govern dormancy and reactivation. Apart from promoting a deeper understanding of malaria relapse, the work will also lead to new imaging methods and is expected to inform new therapeutic strategies.
Objective
What?
Hypnozoites are dormant liver stage malaria parasites that can reactivate and cause repeated blood-stage infections without the bite of an infectious mosquito.
We will, for the first time:
- characterize the cellular environment contributing to dormancy at systems level (WP1)
- explore the reactivation kinetic and tissue environment of hypnozoites within the natural host (WP2)
- functionally characterize host & parasite factors governing dormancy or reactivation (WP3)
Why?
- Dormancy and reactivation of hypnozoites is an unresolved biological mystery since decades
- Dormant parasites are a major obstacle to the curative treatment of malaria
The challenge:
Tracking the in vivo development and understanding the biology of these rare, quiescent parasites that normally reside inside the liver of the host
The solution:
A synergistic, multidisciplinary investigation, which is only possible if we combine the unique resources and complementary expertise of three leading laboratories in:
- Radiopharmaceutical chemistry for the development of dedicated Positron Emission Tomography tracers for non-invasive investigation of the parasites in situ, as well as to capture infected tissue samples for systems level investigations
- Systems biology for simultaneous multi-omics profiling of the parasite and the host cell at single-cell resolution and in the spatial context to be validated by parasitological assays
- Parasitology for functional investigation through genetic engineering and manipulation of the parasites in vitro and validation within the natural host
Anticipated project outcomes:
- Detailed insights into the relapse characteristics of the parasite in vivo
- Understanding how host and parasite factors collectively determine the fate of infection
- Novel imaging, transfection and omics methods for malaria research and beyond
- Opportunities for novel therapeutic strategies for awakening and killing these vicious pathogens
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health scienceshealth sciencesinfectious diseasesmalaria
- medical and health scienceshealth sciencesparasitology
- natural sciencesbiological scienceszoologyinvertebrate zoology
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC-SYG - HORIZON ERC Synergy GrantsHost institution
6525 XZ Nijmegen
Netherlands