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 kinetics and tissue environment of hypnozoites within the natural host (WP2)
• Functionally characterize host and parasite factors governing dormancy or reactivation (WP3)

Why?

• Dormancy and reactivation of hypnozoites is an unresolved biological mystery that has persisted for 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.