Parasite-host interactions regulating dormancy and reactivation of malaria paras...
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 envir...
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 pathogensver más
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