Structural studies of host-parasite interactions at the heart of malaria pathogenicity

Objectives

This research will provide molecular insight into interactions that essential cell surface proteins of the malaria parasites make with receptors from their human host or with inhibitory monoclonal antibodies, thereby guiding immunogen design in vaccine development.

This project targets interactions essential to disease, initially characterising the binding of:

1. Rh5 to basigin, essential in red blood cell invasion by P. falciparum.
2. DBP to DARC, essential in red blood cell invasion by P. vivax.
3. VAR2CSA to chondroitin sulphates, essential in placental sequestration during pregnancy-associated malaria. In each case, we will use the latest tools to determine structures of protein-ligand complexes.

In collaboration with colleagues at the Jenner Institute, Oxford and CMP, Copenhagen it will be raised inhibitory monoclonal antibodies and structurally characterise inhibitory epitopes. This will provide detailed molecular insight to guide the selection or engineering of immunogens that will induce protective immunity against malaria.