Parasite-host interactions regulating dormancy and reactivation of malaria parasites (Host4Hypnozoites)

What?
Hypnozoites are dormant liver stage malaria parasites that can reactivate and cause repeated blood-stage infections without the bite of an infectious mosquito.

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

Project details

Basic Science

Mar 2024 — Feb 2030

$13.61M

The Netherlands