Malaria parasite invasion of the human erythrocyte
The malaria parasite invasion motor and the regulation of actin polymerisation
For the majority of their lifecycle malaria parasites live and replicate within the human erythrocytes, where they cause all of the pathological symptoms associated with malaria disease. Invasion of the human red blood cell is essential to their development. This active process is driven entirely by the parasite using a unique actin-myosin motor. The motor is housed in the parasite pellicle and linked extra-cellularly to the host cell via secreted adhesins on the parasite surface. The power for motility comes from the force of myosin treading along actin filaments, driving the associated complex rearwards, propelling the parasite into the cell. According to this model, actin filaments function as a ‘molecular clutch’ engaging the motor for active invasion. Because the merozoite - the blood stage malaria parasite - invades in a single motion without additional movement, it is the ideal system to study the role of the invasion motor and the underlying mechanics of host-cell invasion in the absence of general gliding motility. To this end we are using cell imaging to piece together the spatio-temporal localisation of the key players of invasion, from actin through to the secreted adhesins (in particular MTRAP) to understand the different stages of invasion in the human malaria parasite Plasmodium falciparum. A significant part of this work is being undertaken in collaboration with the laboratory of Professor Alan Cowman at the Walter and Eliza Hall Institute and Dr Stuart Ralph at Bio21.