Model Advances Research into How Malaria Parasites Invade Red Blood Cells

Using CRISPR-Cas9-mediated receptor gene knockout and lentiviral expression of wild-type and mutant genes, researchers at the University of Bristol and Imperial College London have established a new model system that uses red blood cells grown in the laboratory to study how malaria parasites invade red blood cells. The work was published last week in Nature Communications.

The new cell line can produce unlimited numbers of immature progenitor cells that can be pushed to produce new red blood cells (reticulocytes) in the laboratory. Using these cells, the team was able to show that red blood cells generated using this technique can support both invasion by and intracellular development of Plasmodium falciparum.

By using CRISPR-Cas9 to edit the genome of the immature cells, the team was also able to remove a protein called basigin that is important for invasion and normally present on the surface of red blood cells and show that the reticulocytes generated from this edited line were completely resistant to invasion. Reintroducing the basigin gene into the edited cells restored invasion to normal levels. This work shows that these cells can be used to remove and replace different red blood cell proteins and assess how their absence or alteration affects the ability of the parasite to successfully invade.

"The ability to alter protein expression in the red blood cell and study the effect that these changes have on parasite invasion or development is hugely exciting. This system has opened up many new potential avenues of research that should allow us to better understand the mechanism by which the malaria parasite is able to successfully invade the red blood cell, and the specific roles that host cell proteins play in this process," explained Tim Satchwell, lead author of the study.