Parasite-host interactions regulating dormancy and reactivation of malaria parasites

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