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Tagging Essential Malaria Genes to Advance Drug Development

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Red blood cell infected with malaria-causing parasites

Caption: Colorized scanning electron micrograph of a blood cell infected with malaria parasites (blue with dots) surrounded by uninfected cells (red).
Credit: National Institute of Allergy and Infectious Diseases, NIH

As a volunteer physician in a small hospital in Nigeria 30 years ago, I was bitten by lots of mosquitoes and soon came down with headache, chills, fever, and muscle aches. It was malaria. Fortunately, the drug available to me then was effective, but I was pretty sick for a few days. Since that time, malarial drug resistance has become steadily more widespread. In fact, the treatment that cured me would be of little use today. Combination drug therapies including artemisinin have been introduced to take the place of the older drugs [1], but experts are concerned the mosquito-borne parasites that cause malaria are showing signs of drug resistance again.

So, researchers have been searching the genome of Plasmodium falciparum, the most-lethal species of the malaria parasite, for potentially better targets for drug or vaccine development. You wouldn’t think such work would be too tough because the genome of P. falciparum was sequenced more than 15 years ago [2]. Yet it’s proven to be a major challenge because the genetic blueprint of this protozoan parasite has an unusual bias towards two nucleotides (adenine and thymine), which makes it difficult to use standard research tools to study the functions of its genes.

Now, using a creative new spin on an old technique, an NIH-funded research team has solved this difficult problem and, for the first time, completely characterized the genes in the P. falciparum genome [3]. Their work identified 2,680 genes essential to P. falciparum’s growth and survival in red blood cells, where it does the most damage in humans. This gene list will serve as an important guide in the years ahead as researchers seek to identify the equivalent of a malarial Achilles heel, and use that to develop new and better ways to fight this deadly tropical disease.


Copy-editing the Genome: Extreme Personalized Medicine?

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COOL TOOL. See how the TALE protein (rainbow colored) recognizes the target DNA site and wraps around the double helix. When this TALE protein is fused to a nuclease (the scissors), creating a TALEN, the hybrid protein will clip the DNA at the target site. Credit: Jeffry D. Sander, Massachusetts General Hospital

If I made a spelling mistake in this blog, and you were my copy editor, you’d want to fix it quickly. You’d delete the wrong letter and insert the correct one. Well, DNA is a language too, with just four letters in its alphabet; and disease can occur with just one letter out of place if it’s in a vulnerable position (think sickle cell anemia or the premature aging disease, progeria). Wouldn’t it be great for tomorrow’s physicians to be able to do what the copy editor does? That is, if they could fix a genetic mutation quickly and efficiently, without messing up the rest of the text?