The Plasmodium pir gene family: chronic infection, immunity and virulence.

Malaria parasites carry a large family of genes called *pir* that help them survive inside a host, and this project will work out exactly how those genes do it. The problem is that *pir* genes are poorly understood. They are found in all malaria parasites, including *Plasmodium falciparum* which causes the deadliest form of human malaria, but no one knows whether they drive severe disease, help the parasite hide from the immune system, or allow it to cause long-lasting chronic infections. Without this knowledge, efforts to design vaccines or drugs that target these genes are flying blind. This project uses a mouse malaria model to answer five specific questions: which *pir* genes different rodent parasites carry, how the genes are switched on and off during an infection, where the resulting proteins sit inside the parasite, whether those proteins physically grab onto host molecules, and how all of this links to the severity of disease and the host's immune response. The research is fundamental science. It will not produce a new drug or vaccine tomorrow. But understanding how *pir* genes work could eventually reveal a new weakness in the malaria parasite—one that might be exploited to block transmission, prevent chronic infection, or reduce the severity of disease in the millions of people who get malaria each year.