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A team of researchers from Harvard and the Broad Institute at MIT identified 11 genes that are implicated in the malaria parasite’s notorious ability to rapidly evade drug treatments—a discovery that could revolutionize malaria treatment.
For the study, the team used gene-hunting technology to search the genetic code of 57 different parasites from three different countries.
They found 11 genes that aid in drug resistance—one of which was previously confirmed and 10 that were discovered for the first time. A parasite that was still vulnerable to drugs became much more resistant to treatment when it was injected with PF10_0355, one of the newly discovered drug resistant genes.
This suggests that the gene may play a crucial role in building drug resistance among parasites, said Daria N. Van Tyne, one of the study’s authors from the Harvard School of Public Health.
“We feel that this is one gene of potentially many that affect drug-resistance mechanisms,” Van Tyne said. “We’re now working to follow up and understand how these and the other genes identified work.”
Currently, malaria affects more than 240 million people around the globe and kills 850,000 every year, especially in Africa, Asia, and South America. Reducing the toll of malaria is a major challenge because of the parasite’s talent for swiftly developing resistance to multiple drugs.
By identifying the mutations associated with drug resistance, scientists can better understand how parasites evade the drug, according to Sarah K. Volkman, senior research scientist at the Harvard School of Public Health’s Department of Immunology and Infectious Diseases.
“Once we understand the processes used by the parasite to avoid the effects of the antimalarial treatment, scientists can develop new drugs that circumvent the strategies employed by the drug-resistant malaria parasite,” Volkman said.
With the success of their work—which took over two and a half years to complete—the scientists plan on continuing their collaboration. They are currently investigating ways to develop a surveillance system that will contain a battery of genetic markers that tag resistance to different drugs.
“If a patient came in, they could look at the genetic code of the parasites and determine which drugs would be most effective in treatment,” Assistant Professor of Organismic and Evolutionary Biology Pardis C. Sabeti said. “It was not surprising that we found the existence of malarial-resistant genes. What was surprising was that we found them all within such a small sample of only 57 parasites.”
Much of the discovery was attributed to the technology used. The scientists used a genome-wide association study to look at the entire sequence of the parasite’s genome. Sabeti, who contributed to the computational genetics component of the collaboration, said that this technology allowed the researchers to analyze every single nucleotide of the sequence—24 million in total.
This application of genetic manipulation has rarely been applied to parasitic research.
Professor Dyann F. Wirth, director of the Harvard Malaria Initiative at the Harvard School of Public Health, said that most people who study genomes do not come from a microbiology background.
“It takes a while for them to adjust to changes in the way they think about the world,” Wirth said.
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