Science, Technology and Engineering

Maier Laboratory

Department of Biochemistry

Research - Molecular Mechanisms of Malaria Pathogenesis

The focus of Dr. Maier's research is the identification of proteins involved in malaria pathogenesis and the elucidation of their function through biochemical, molecular and cell biological means.

Malaria - the problem

Malaria is a life-threatening parasitic disease transmitted from person to person through the bite of a female mosquito. Over 40% of the world's population is at risk and there are at least 500 million cases of acute malaria each year. The majority of fatalities are children under the age of 5 - every 30 seconds a child dies of a malaria infection. The estimated economic burden of malaria for Africa alone is more than US$12 billion annually. Despite large-scale international efforts of malaria eradication, the number of cases has dramatically increased over the last decades.

Malaria in humans is caused by 4 species of single-celled Plasmodium parasites, of which Plasmodium falciparum causes the most serious disease. Malaria is found in other animals as diverse as monkeys, mice, bats, penguins or lizards, caused by a wide range of different Plasmodium species.

Immunity to Plasmodium falciparum malaria takes years to develop and is never complete. The repertoire of effective anti-malarial drugs is dwindling due to emergence and spread of drug resistance. Therefore the demand for effective, safe, affordable and easy to administer intervention strategies is higher than ever before.

Plasmodium falciparum - the organism

Giemsa-stained blood smear showing P. falciparum parasites of different stages. inside human red blood cells.

Plasmodium falciparum is not only the causative agent of the most severe form of malaria, but also a fascinating and intriguing organism. Some of its interesting hallmark features are:

Research focus

The projects in our group revolve around the following areas:

1. Function of molecular chaperones in the export and display of parasite proteins

2. Erythrocyte membrane modifications during malaria infection

Scanning electron micrograph of human red blood cells infected with knob-producing and knob-deficient Plasmodium falciparum lines. (Courtesy of Dr. Melanie Rug, WEHI, Melbourne)

Infection with the malaria parasite Plasmodium falciparum causes modifications of the erythrocyte membrane composition and rigidity. In particular protrusions of the red blood cell membrane are induced – so called knobs. These knobs are believed to provide an elevated platform and anchor point from which a major virulence factor is sticking out. This virulence factor attaches to the wall of blood vessels and prevents the infected red blood cell to be flushed into the spleen, where it would be destroyed. Therefore the display of this virulence factor is essential for the survival of the malaria parasite in the human body. At the same time the adhesion of infected red blood cells causes obstructions of blood vessels, which accounts for many symptoms of a malaria infection. We have recently identified key molecules that are important for the formation of knobs. With the aid of reverse genetics we try to understand their function and mechanism.

3. Molecular tools to reveal protein function and identify drug targets

Advances in malaria research are hindered by the relatively small inventory of available molecular tools. Culturing and genetic manipulation are quite demanding and cumbersome in comparison to other organisms. Major discoveries very often go hand in hand with the application and development of new techniques. We strive to make a contribution to the repertoire of available techniques.

Collaborators on these projects include Dr Melanie Rug, Prof. Alan Cowman (The Walter and Eliza Hall Institute of Medical Research, Melbourne), Dr Nick Klonis and Prof. Leann Tilley (La Trobe University).