From the parasites in patients' blood, the researchers simultaneously measured the activity level, or "expression", of every P. falciparum gene. Co-author Elizabeth Winzeler, an associate professor at The Scripps Research Institute, led this aspect of the study. "The ability to look across the parasite's entire genome was essential," said Winzeler. "We uncovered extraordinary things about parasite biology -- things we could not have even imagined."
Winzeler, who is also head of malaria research at the Genomics Institute of the Novartis Research Foundation (GNF), where much of the genomic work was performed, is grateful that organizations like GNF choose to encourage these types of high-risk studies. "We are especially excited about using these observations to guide our drug discovery efforts," she said.
The key to interpreting these results lay in two computational tools, first developed by Mesirov and her colleagues to study the genomics of human cancer cells. By adapting these tools for malaria, the researchers were able to identify distinct groups of parasites, each marked by characteristic sets of active and inactive genes. The biological underpinnings of these groups were made clearer through a second innovative approach: systematically comparing P. falciparum -- whose genes and genome are poorly understood -- to the baker's yeast, an organism that has been extensively characterized at the genetic level. Since the malaria parasite and the baker's yeast are both single-celled eukaryotes, it is possible they may share some of the same cellular machinery and could also respond in some similar ways to their surroundings.
With this unusual approach, co-senior author Regev and her colleagues were able to describe three different classes of parasites, one of which displayed features as
|Contact: Nicole Davis|
Broad Institute of MIT and Harvard