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Malaria Parasite Gene Chips
By Kate Dalke

Using a new gene chip, scientists have suggested the function of over 1,000 genes in a common malaria parasite. These genes could someday be used as targets for new drugs or vaccines against the disease.

A group led by Elizabeth A. Winzeler at the Scripps Research Institute in La Jolla, California, has published this research in Science.

Parasites in red blood cells during different stages of their life cycle in humans: trophozoite, schizont, and ring stage (left to right).

Meanwhile, another research team from the University of California, San Francisco, (UCSF) says it will publish similar data online in the Public Library of Science later this month. PloS is a nonprofit organization founded to promote open and free access to scientific articles.

The genome sequence of Plasmodium falciparum, which causes the most severe malaria, was published in October 2002—but the functions of most of its genes remain unknown.

The genetics of malaria parasites are notoriously difficult to study. The single-celled organisms have a complex life cycle, which includes replication in mosquitoes and infection of liver and red blood cells in people.

In the Science study, the researchers used a custom-made gene chip to analyze the expression of parasite genes during nine different stages of the parasite’s life cycle.

Genes with similar functions turned “on” and “off” at the same time and were therefore grouped into a specific cluster. These clusters also contained unknown genes that could be assigned a function based on known genes in the cluster—a sort of guilt by association.

“Proteins that had a role in a defined process tended to segregate together,” says Winzeler.

For example, the 37 genes known to be involved in red blood cell invasion all had similar expression patterns. Most of these are under investigation as vaccine targets.

The researchers report that nearly 100 other genes also fit into the same blood-cell invasion cluster and could therefore be new candidates for vaccines.

“Up until this point, it’s been a hunt-and-peck process to determine proteins involved in the parasite’s invasion process,” says Daniel J. Carucci of the Naval Medical Research Center in Silver Spring, Maryland, who was a member of the research team.

The researchers are now collaborating with scientists who work in regions where malaria is endemic, in an effort to use the gene chip to evaluate how the parasite’s genes may vary between different isolates in different parts of the world.

Joseph DeRisi and his colleagues at UCSF plan to publish their research, in which they used their own DNA microarray of the parasite’s genome, online at PloS and in the inaugural print issue of PLoS Biology in October 2003.

“We felt very strongly that our paper should be in an open-access journal, thus providing free access to the data and manuscript,” says DeRisi, who adds that his research should not be the property of another corporation or organization.

“This is important considering the bulk of malaria researchers in the world are not from first-world countries and often cannot pay the high cost of access to a closed-access journal like Science,” he says.

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Le Roch, K.G., et al. Discovery of gene function by expression profiling of the malaria parasite lifecycle. Sciencexpress. Published online July 31, 2003.
Gardner, M.J., et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498-511 (October 3, 2002).

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