Blackman lab Malaria Biochemistry Laboratory
: Areas of interest
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Malaria is directly responsible for around half a million deaths per annum worldwide, causing terrible suffering and imposing an immense economic burden on much of the developing world.
There is no malaria vaccine, and resistance against mainstay antimalarial drugs is widespread. There is a need to find new ways to treat and control this devastating disease.
The malaria parasite infects and divides within red blood cells. The infected red cell eventually ruptures in a process called egress, releasing a fresh wave of parasites which rapidly invade new red cells. Invasion involves the activity of a complex set of proteins that are released onto the parasite surface to bind to the new red blood cell and penetrate it.
Our work aims to improve our understanding of how these parasite proteins interact with the host red blood cell to enable invasion, and how antibodies can interfere with this process. This will help the development of new drugs and aid vaccine design.
In addition, we are studying a family of parasite-derived enzymes that regulate egress of the parasite from red blood cells, and also modify the parasite surface to prime it for invasion. We are investigating the regulation, structure and function of these enzymes, and searching for inhibitory compounds with potential to be developed as antimalarial drugs.
Figure 2: Depiction of the role of a malarial protease called SUB1 in surface modification and release of malarial merozoites from the infected red blood cell. SUB1 is initially stored in small organelles called exonemes (A). Just before rupture of the host cell, SUB1 is released into the parasitophorous vacuole space (B), where it processes parasite surface proteins and activates a second putative protease called SERA6, leading to rupture of the parasitophorous vacuole and host cell membranes (C).
Figure 1: Atomic structure of a conserved domain from a malarial red blood cell-binding protein called EBA–175. The image shows a cartoon representation of the EBA–175 .region VI crystallographic dimer, with a corresponding surface mesh illustrating the hydrophobic interface between the monomers
