New drugs and vaccines against malaria

Malaria is responsible for around 500,000 deaths annually and enormous morbidity. Current progress in controlling the disease is at risk due to the emergence of resistance to current front-line drug therapies and vector control strategies. There is a pressing need for new therapeutic strategies to target the malaria parasite. We are exploring two strategies to meet this need: new drugs, with new modes of action, and new vaccine antigens based on disordered proteins on the parasite surface. Projects are available in either of these areas. As part of our drug discovery pipeline, we have identified benzimidazoles acting by two different malaria pathways. One of these has a defined target, that we interrogate with our expertise in medicinal chemistry and structural biology. The other acts via an as-yet-undetermined mechanism of action.

We aim to make a series of these compounds and test them via our biophysical and metabolomics techniques. This will aid in a greater understanding of the mechanism of action of these potent antimalarials, which are of urgent need. Proteins that lack a well-defined three-dimensional structure are termed disordered proteins. Such proteins are abundant in the malaria parasite, and many are important targets of the protective immune response to malaria. The unique structural properties of these proteins make them attractive vaccine antigens, but the implications of these properties are not yet well understood. By better understanding these implications, we are designing more effective antigens for inclusion in a future malaria vaccine.