Malaria is caused by a parasitic protozoan that invades red blood cells, where it develops and multiplies before bursting out and invading new red cells. This cycle is responsible for the disease.
There is much interest in understanding the interaction between the parasite and the host immune system, to contribute to the development of a malaria vaccine. The identification of new targets for drugs to kill the parasite and interrupt the cycle of multiplication offers the potential of much needed new therapeutic interventions.
In one project, focused on how the parasite invades host cells, we study the actomyosin-based motor that drives invasion. We have shown that an unusual calcium-dependent protein kinase phosphorylates two of the proteins in the motor complex, a process that may be important in its assembly. Together with colleagues at MRC Technology we have identified chemical compounds that inhibit this kinase and kill the parasite at very low concentrations. These compounds have the potential to be developed into drugs against malaria and are powerful reagents to dissect the exact role of this kinase in the parasite's biology.
Figure 1: Within the parasite's cycle of invasion and development we study several aspects of its cell biology and biochemistry to understand the complex interaction between parasite and host.(Click to view larger image)
Figure 2: Location of an apical rhoptry protein (RhopH2), an invasion motor protein (GAP45) and a surface protein (MSP1) in merozoites within a schizont. (Click to view larger image)