The malaria parasite has been studied for decades, but surprisingly, little is known about how it behaves in humans to cause disease. In a groundbreaking study published November 28 in the advance online edition of Nature, an international research team has for the first time measured which of the parasite's genes are turned on or off during actual infection in humans, not in cell cultures, unearthing surprising behaviors and opening a window on the most critical aspects of parasite biology.
That insight springs from the genomic analysis of parasites in their natural state, derived directly from patients residing in Senegal, and also from the researchers' use of innovative computational approaches to interpret their results. These computational methods helped to identify three distinct biological states of the malaria parasite: an active growth-based state, a starvation response and an environmental stress response, presumably related to the body's inflammatory response to the parasite. This physiological diversity was previously unknown and may help explain the widely varying course of the disease in different patients, from mild, flu-like illness to coma and even death.
"For the first time, we have glimpsed the biology of the malaria parasite in one of its most important environments -- humans," said co-senior author Aviv Regev, a core member of the Broad Institute of MIT and Harvard and an assistant professor of biology at MIT. "Our unique computational approach holds promise not only for understanding the malaria pathogen, but likely other important microbes as well."
"This work illustrates the true power that comes from developing the right computational methods and applying them to important biomedical problems," said co-senior author Jill Mesirov, director of Computational Biology and Bioinformatics at the Broad Institute of MIT and Harvard. "Even more importantly, it reflects scientific research at its best -- a global effo
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Broad Institute of MIT and Harvard