Science, Technology and Engineering

Department of Biochemistry
Malaria Research at La Trobe University

Malaria is a lethal parasitic disease affecting millions of people in the tropical and sub-tropical regions of the world. Each year, about 500 million people become infected with malaria and 2-3 million people, mostly children, die from complications of the disease. In addition to the deaths, malaria debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. Plasmodium falciparum is the most virulent of the human malaria parasites and is responsible for more than 90% of malaria cases in countries such as Africa.  As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. New antimalarial drugs are required to replace the currently failing armoury of therapeutic agents and, in the longer term, a malaria vaccine is desperately needed.

At La Trobe University, we have a number of groups working on different aspects of malaria research. Work in the laboratory of Professor Robin Anders is focussed on potential vaccine antigens from the asexual blood stages of Plasmodium falciparum. Workers in Professor Leann Tilley’s and Dr Nick Klonis’ laboratory aim to understand the interactions of the malaria parasite with the erythrocytes of its human host, with a view to developing new antimalarial therapeutics. They are using confocal microscopy, optical spectroscopy and fluorescence photobleaching techniques to study the dynamics of different parasite components. Associate Professor Mick Foley’s laboratory is using the powerful phage display approach to identity peptides that interact with a number of important malaria proteins.

The team around Dr Alex Maier is using genetic approaches to identify and characterize Plasmodium molecules involved in host cell modification. These modifications are the basis of various symptoms of the malaria infection. Understanding these processes will open up new avenues of intervention.
 

Left hand panel: Diagrammatic representation of a parasitised erythrocyte. The parasite resides within a parasitophorous vacuole (PV) within the host erythrocyte. Proteins are exported from the parasite to the erythrocyte cytosol to modify the properties of the host cell. The PV appears to have sub-compartments, possibly formed by close apposition of the parasite plasma membrane with and PV membrane, while extensions of the PV form a tubulovesicular network (TVN). Maurer's clefts are parasite-derived compartments just underneath the erythrocyte membrane.

Middle panels: Differential interference contrast images and fluorescence micrographs of transfected malaria parasite-infected erythrocytes. The parasites are expressing a chimera of GFP (green fluorescence) with the N-terminal region of the exported protein-1. The cells were co-labelled with BODIPY-TR-ceramide (red fluorescence) to label the lipid compartment (see Adisa et al. (2003) Journal of Biological Chemistry 278: 6532-6542). The signal sequence of exported protein-1 directs the green fluorescent protein to the parasitophorous vacuole of transfected malaria parasites.

Right hand top panel: Ratiometric image of a parasitised erythrocyte labelled with the lipid probe Nile Red.

Right hand lower image: Transfected malaria parasite-infected expressing a chimera of GFP with a protein that is partly exported to the erythrocyte cytosol.