Studying Malaria Parasite Liver Infection to Discover Novel Anti-Malaria Interventions

Inside the hepatocyte, a single sporozoite will develop into thousands of merozoites and hide from the immune system. The liver merozoites will eventually exit the liver, enter the bloodstream and infect erythrocytes (red blood cells). This step initiates the life-threatening, clinical phase of P. falciparum infection known as malaria.

The liver stage of Plasmodium infection is the only path through which parasites must pass to infect red blood cells and also be successfully transmitted back to mosquitoes. The liver stage is therefore an ideal point for developing new anti-malarial solutions that prevent downstream malaria from establishing, and is also a fantastic target to stop malaria parasite spread by mosquitoes. Primary human hepatocytes are the natural target cells for sporozoites and they permit high levels of infectivity (5-20%), support the normal replication of parasites in the thousands per cell and can allow many different research approaches.

These features make primary human hepatocytes the gold standard for investigating malaria parasite liver infection biology, and for underdtanding the usefulness of drugs and optimizing vaccine development on liver stages. Therefore, the Malaria Research team at The Walter and Eliza Hall Institute (WEHI) have teamed up with the Hepatobiliary surgeons at St Vincent’s Hospital Melbourne to provide viable liver tissue for medical research.

Aim:

• To study the liver stage of infection by human Plasmodium parasites to better understand the biology of infection, identify novel therapeutic and vaccine targets and assess antimalarial drugs currently in development at WEHI.