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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.


Using Genomics to Follow the Path of Ebola

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Ebola virus

Caption: Colorized scanning electron micrograph of filamentous Ebola virus particles (blue) budding from a chronically infected VERO E6 cell (yellow-green).
Credit: National Institute of Allergy and Infectious Diseases, NIH

Long before the current outbreak of Ebola Virus Disease (EVD) began in West Africa, NIH-funded scientists had begun collaborating with labs in Sierra Leone and Nigeria to analyze the genomes and develop diagnostic tests for the virus that caused Lassa fever, a deadly hemorrhagic disease related to EVD. But when the outbreak struck in February 2014, an international team led by NIH Director’s New Innovator Awardee Pardis Sabeti quickly switched gears to focus on Ebola.

In a study just out in the journal Science [1], this fast-acting team reported that it has sequenced the complete genetic blueprints, or genomes, of 99 Ebola virus samples obtained from 78 patients in Sierra Leone. This new genomic data has revealed clues about the origin and evolution of the Ebola virus, as well as provided insights that may aid in the development of better diagnostics and inform efforts to devise effective therapies and vaccines.