Researchers unravel genomic mystery of malaria’s deadliest parasite

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Credit: Aaron Hilf

Ninety-percent of people killed by malaria are infected with the parasite Plasmodium falciparum. Now, for the first time, researchers have learned exactly what is essential in the parasite's genetic makeup, paving the way to the development of stronger antimalarial drugs.

A research team led by public health scientists at the University of South Florida in Tampa created a new technique that mutated most of P. falciparum's 6,000 genes, providing a far superior understanding of how each gene functions. In the study published in Science, the authors successfully targeted adenine and thymine, two of the four chemical building blocks that make up DNA. This is significant as P. falciparum's high percentage of adenine and thymine previously limited efforts to manipulate the parasite's genome, resulting in only a few hundred mutant strains.

"This is a transformative advance," said lead author John H. Adams, PhD, Distinguished Professor, University of South Florida College of Public Health. "The genome of this malaria parasite has been resistant to most methods in the modern genetics toolbox. Consequently, functional importance of only a few hundred genes was determined. Using piggyBac mutagenesis, our new genetic tool, we have functionally characterized nearly all of the parasite's genes. Identifying essential genes and pathways will help guide and accelerate future drug and vaccine development."

With funding from the National Institutes of Health (NIH), the research team used advanced computational analyses to identify about 2,600 genes that are essential to the parasite's growth and resistance to antimalarial drugs. This critical information is expected to have a dramatic impact on the fight against malaria, which infects 220 million people worldwide and claims 500,000 lives each year.

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