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Gene expands malaria's invasion options

The malaria parasite Plasmodium falciparum uses different pathways to invade red blood cells, evading the body's immune system and complicating efforts to create effective vaccines against the disease. A research team led by Australia's Alan F. Cowman, an international research scholar with the Howard Hughes Medical Institute, has identified a gene that the parasite uses to switch back and forth between invasion pathways.

Researchers from the Scripps Research Institute in La Jolla, California, and the Genomics Institute of the Novartis Research Foundation in San Diego contributed to the work, which was published in the August 26, 2005, issue of Science, P. falciparum causes the most lethal form of malaria, which results in one million deaths a year worldwide.

Some P. falciparum strains invade red blood cells via protein receptors on the surface that contain a sugar known as sialic acid. If scientists treat blood cells with an enzyme to remove sialic acid, the parasite can no longer invade. Other strains including one called W2mef can invade using the sialic acid receptors, but also have the ability to switch to other pathways if necessary.

"It's a bit like someone trying to get into a house with different doors," says. Cowman of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and the study's senior author. "When you remove sialic acid, you block half the doors. W2mef normally goes in through the receptors with sialic acid, but it can switch so it has two methods of entry."

To investigate how the parasite manages to switch to an alternative mode of blood cell invasion, Cowman and colleagues produced lines of the W2mef parasite that used sialic acid for invasion, and lines that could invade without it. Then they compared the differences in gene activity between the two types and identified two genes that warranted further study.

The team found only two genes whose activity diffe
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Contact: Brad Allen
allan@wehi.edu.au
61-393-452-345
Research Australia
26-Aug-2005


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