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

My 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. Surface proteins mediate essential steps in the parasite life cycle, including sequestration from spleenic clearance and host cell invasion. They must balance conflicting selection pressures, maintaining interactions while diversifying to aid immune evasion. Structural studies will allow us to map polymorphisms onto molecular surfaces while identifying conserved binding sites and inhibitory epitopes on which to focus immune recognition. We will target 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 place ntal 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 we will raise 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.