Research Insights

Malaria is a serious disease caused by the parasite Plasmodium, which initially infects liver cells before spreading to red blood cells and causing a potentially lethal infection. Traditionally, this early liver stage was considered to be relatively invisible to the immune system. However, recent studies, including our own, have found that liver cells can detect and respond to Plasmodium using their natural immune defenses. When Plasmodium enters liver cells, the cells recognize the parasite’s presence and activate a chain of immune responses. These responses include producing reactive molecules, recruiting cellular machinery to attack the parasite’s protective bubble, and eventually breaking it down. As the parasite’s barrier is compromised, its DNA is exposed, triggering further immune actions that lead to the destruction of the infected liver cells. Together, these actions help control the parasite in the liver. However, Plasmodium can still survive in a small portion of liver cells, allowing it to continue its life cycle and eventually spread to the blood. This is enough to cause a potentially lethal malaria infection. We believe that Plasmodium uses special proteins we call ‘exported effectors’ to counteract the liver cell’s defenses, helping it evade destruction in these few cells. Our research aims to identify these protective proteins from Plasmodium and understand how they work. Our approach includes systematically identifying these parasite proteins, studying their behavior, and exploring how they interact with the mediators of liver cell defenses. By uncovering these survival tactics, we hope to find new ways to prevent the parasite from neutralizing our liver cells’ defenses, allowing the liver cells to clear the parasites more effectively.

Funder: Burroughs Wellcome Fund

Amount: $505,000

PI: Samarchith Kurup, Franklin College of Arts & Sciences, Department of Cellular Biology