Malaria parasite's boxful of disguises exposed

Friday, April 8th 2005

Teams led by Professor Alan Cowman and Dr Brendan Crabb at The Walter and Eliza Hall Institute of Medical Research (WEHI) have discovered how the malaria parasite, Plasmodiumfalciparum, uses genetic trickery to evade the human body's immune system. This discovery may assist in the eventual development of drugs that disrupt the parasite's ability to disguise itself, therefore leaving the parasite open to detection and destruction.

When the parasite invades the body, the host raises an immune response. Sometimes the host's antibodies manage to bind to the parasite and destroy it. Often, however, the parasite resorts to "masquerade" tactics, disguising its true nature within the biological environment. Until now, exactly how that masquerade actually works has been a mystery.

The Cowman and Crabb teams have discovered how the parasite can choose from 60 genes - or different forms of disguise - in its quest to fool the host's immune system. At any time, the parasite has the ability to select one of those 60 genes to create a surface protein mask. The parasite manages to keep the other 59 genes inactive or "silent" by wrapping them in tight bundles. After a certain interval, the parasite removes the active masking gene and randomly selects another from the bundles to express on its surface, preserving its disguise.

Professor Cowman comments, "Now that we have revealed the parasite's mysterious mechanism of disguise and survival, scientists can look forward to designing molecules or drug candidates that will upset the successful masquerade. We hope that kicking over that boxful of 60 disguises will leave the parasite revealed for what it really is, enabling the immune system to identify the target and move in for the kill."

Other members of the discovery team are Manoj Duraisingh, Till Voss, Alison Marty, Jennifer Thompson, Robert Good and Michael Duffy (The University of Melbourne).

The research was funded by the National Health and Medical Research Council of Australia (NHMRC), the Howard Hughes Medical Institute (HHMI) and the Wellcome Trust. Professor Cowman and Dr Crabb are HHMI international research scholars at WEHI.

The research paper is published in the 9 April 2005 issue of the prestigious journal Cell.

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