ProjectsUnderstanding Malaria Parasites “bottom-up”
Malaria is a disease caused by unicellular parasites that infect red blood cells and has killed more humans in history than any other disease. Currently over 200 million people are still infected every year and nearly half a million die of the diseases. The disease is caused by at least 6 different parasites, although the main burden comes from infections with Plasmodium falciparum. Malaria parasites do also infect a wide range of animals including lizards, birds and rodents. Malaria parasites are transmitted by mosquitoes and pass through a number of different stages on their complex route along their life cycle. Hence, while all parasites can infect red blood cells, there is considerable variability from species to species at different stages. For example, parasites first replicate in mammals (but not birds) inside the liver, where they form the red blood cell infecting forms. Yet, in the second most important human-infecting parasite Plasmodium vivax, parasites can also undergo a switch to quiescence in the liver and stay dormant for years before they produce red blood cell infecting parasites. Little is known about this quiescent stage of the parasite. Once these parasites enter red blood cells they show different tropisms, with P. vivax preferably infecting young red blood cells and P. falciparum being promiscuous in its choice. Once inside the red blood cells, P. vivax does not change the physical parameters of the host cells, while P. falciparum infected red cells stiffen considerably. Many more such differences exist along the life cycle with their different forms. Usually Plasmodium parasites are investigated by deleting or modifying genes of interest in a classic reverse genetic approach. We propose here to investigate selected mechanisms of the parasites that differ between Plasmodium species by complementing the parasites that do not show certain characteristics using both rodent- and human-infecting malaria parasites.