‘SERA6 and SUB1 have been found to be essential for the malarial parasite to break through the internal compartment of the red blood cells. This discovery has opened new avenues to target these two proteins to develop effective antimalarial drugs.’
In order to escape red blood cells, the parasites have to break through both the internal compartment and the red cell membrane
The research team used genetic knockout experiments to show that a protein called SUB1 is essential for the parasite to break through the internal compartment, while SERA6 - which is activated by SUB1 - is essential for the parasite to break through the red blood cell membrane.
"Over 400,000 people die of malaria each year, and resistance to common antimalarial drugs is growing," says Professor Mike Blackman, Group Leader at the Francis Crick Institute, who led the research. "We're studying the deadliest malaria parasite, Plasmodium falciparum, to try to find new drug targets that work in a different way to existing treatments."
In the latest study, the team have identified two key proteins that malaria parasites need to escape red blood cells and infect fresh cells. The research was done in collaboration with the Proteomics Science Technology Platform at the Crick as well as scientists at Birkbeck College, King's College London and the London School of Hygiene & Tropical Medicine.
"We've already started collaborating with GSK to see if designing drugs that target these proteins could form the basis of a new antimalarial drug," says Dr. James Thomas, Crick postdoctoral scholar and joint first author of the paper.
Using analytical tools, the team then figured out how SERA6 breaks through the blood cell membrane. Crick Ph.D. student and joint first-author Michele Tan explains: "There is a strong chicken wire-like meshwork that sits under the red blood cell membrane to provide strength and support. We found that SERA6 cuts the chicken wire, causing the blood cell membrane to collapse and rip open so that the parasites can escape."