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Largest synthetic gene ever built offers insights into anti-malarial drug resistance

Researchers at Georgetown University Medical Center say they are moving closer to understanding why the most lethal form of human malaria has become resistant to drug treatment in the past three decades. They have been able to artificially construct, and then express in yeast, a protozoan gene that contributes to such resistance. And it was no small feat. The gene they laboriously constructed over a two-year period is believed to be the largest synthetic one ever built, and it successfully produces large quantities of the encoded protein, whose function can now be easily studied.

In research published in the May 22 issue of the journal Biochemistry, the researchers say that with the addition of the recreated gene, PfMDR1 and its protein, they have all the biomolecular tools necessary to molecularly understand how the malarial parasite Plasmodium falciparum (P. falciparum), has become resistant to most of the drugs that could once destroy it. They have already described and expressed two other genes known to confer drug resistance.

"Now that we have these genes expressed in a convenient yeast system, we can work to understand the molecular basis of anti-malarial drug resistance, providing insight into how future drugs might be designed to effectively kill the parasite," said Paul Roepe, Ph.D., a professor in the Department of Biochemistry and Cellular & Molecular Biology as well as the Department of Chemistry.

Any animal with red blood cells can develop malaria, which is caused by a single-cell protozoan parasite transmitted by the bite of the female Anopheles mosquito. There are about 160 different species of malaria parasites, according to Roepe. Five infect humans, but P. falciparum is responsible for about 1 million deaths out of 300 million acute cases of infection each year. Most of these deaths occur in young children living in sub-Saharan Africa.

Roepe and his collaborators at Georgetown University, in collaborat
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Source:Georgetown University Medical Center


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