Scientists are making strides in understanding how the malaria parasite Plasmodium falciparum disguises itself to avoid detection by the immune system. The findings could lead to the development of new drugs for a disease that causes more than 300 million acute illnesses and at least one million deaths each year, most of them in developing countries.

Individuals infected with malaria cannot develop an effective immune response because the parasite that causes the disease is a master of disguise. Throughout its lifetime, P. falciparum continually changes the version of a protein known as PfEMP1 that it deposits on the surface of infected cells. By the time the immune system learns to recognize the protein and starts making antibodies against it, the parasite has switched to another form of the protein, and the game of hide and seek starts over.

In a new study, scientists led by Alan Cowman and Brendan Crabb, Howard Hughes Medical Institute (HHMI) international research scholars at The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, set out to test the hypothesis that P. falciparum uses gene silencing to mask its presence. Their findings are published in the April 8, 2005, issue of the journal Cell. The study also involved researchers from Monash University in Clayton, Australia, the University of Melbourne, and the Institut Pasteur in Paris.

Since the mid-1990s, researchers have known that a family of genes known as var encode PfEMP1. While the parasite's genome contains at least 50 var genes, only one is expressed at any given time, giving rise to a single version of the PfEMP1 protein. Over the course of an infection, expression switches from one var gene to another a phenomenon that until now, scientists have not understood.

The researchers say that teasing out the mechanism by which the var genes are switched on or off could lead to the development of novel drugs for malaria. "If you could work out a
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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
7-Apr-2005

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