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Fighting Malaria On His Home Turf
by Shelley DuBois
Surface protrusions, called knobs, on Plasmodium falciparum-infected red blood cells display aggregates of PfEMP1, a protein that shuts down part of the immune system alarm pathway. The smooth appearance of the red cell on the right is due to a mutation in another protein, KAHRP, required for knob formation.
For Louis Schofield, the malaria problem in Papua New Guinea is more than a passing interest.
When he was a boy, his family lived on the Pacific island, where his father worked as a physician treating patients with tropical diseases such as dengue fever, typhoid, and malaria. Schofield says, “I got both metaphorically and literally exposed to some of those infections. I have no doubt that it planted some seeds in my mind.”
Now at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia, Schofield has merged his laboratory studies with field trials involving children in Papua New Guinea to better understand how molecules in mosquito-borne protozoa make malaria so difficult for the human immune system to fight.
“Malaria causes more than a million fatalities every year, mainly in kids,” Schofield says. “I believe strongly that inappropriately regulated immunological reactions are responsible for a lot of those fatalities. So the thing is to identify the parasite molecules that alter the immune response.”
Most recently, Schofield and Alan Cowman, both HHMI international research scholars at WEHI, found the molecule used by Plasmodium falciparum—the protozoa that causes the deadliest form of malaria—to turn off the body's immune response.
Typically, a protein known as interferon-gamma (INF-gamma) alerts white blood cells when a pathogen enters the body. But when P. falciparum protozoa infect a red blood cell, they send a molecule called PfEMP-1 to the surface of the cell. PfEMP-1 shuts down the INF-gamma alarm pathway.
In 2002, Schofield discovered how another malaria parasite molecule called GPI triggers an inflammatory response in the body, sometimes with fatal side effects. He and his team suspected that other parasite molecules also contributed to skewing the balance of the immune system. They set their sights on PfEMP-1 because they knew it mediates contact between parasites and white blood cells.
Image: Ross Waller and Alan Cowman