Toxoplasma: Sphingolipids in host-parasite interactions syntheses versus scavenging

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The apicomplexans are a large group of related, single-celled microscopic organisms that cause a range of diseases (including malaria) in both humans and economically important domestic animals. One of these, Toxoplasma gondii, can infect most species of warm-blooded animals causing a disease known as toxoplasmosis. In recent times Toxoplasma has come to prominence as causing serious diseases in patients whose defences (immune response) against such invading organisms have been damaged, such as those suffering from acquired immunodeficiency syndrome ¿ AIDS. In addition, infection of unborn lambs with Toxoplasma is a major cause of miscarriage, leading to annual multi-million pound losses to UK sheep farmers. Humans and other animals usually become infected with Toxoplasma following ingestion of contaminated food or faeces. Subsequently, the parasites can invade almost any of the cells that make up the body of an animal. However, in most cases this infection does not cause serious disease, instead Toxoplasma is controlled by the immune response of the animal and retreats into cysts in the brain or in muscle tissue. These cysts can remain throughout the animal¿s life without causing any problems. However, a damaged (in an AIDS patient) or undeveloped (in an unborn animal) immune response is unable to control the parasite in this way leading to disease. Within the animal cell Toxoplasma manufactures many substances it needs for growth, however, it is also able to scavenge various materials that it uses for its own purposes. This research proposal aims to investigate how the parasite manufactures or acquires an important component of its plasma membrane (a fatty barrier that separates the inside of the parasite cell from the external environment) ¿ sphingolipid. This will help us understand how Toxoplasma grows within animal cells and how it subsequently causes disease. In addition, the observation that some of the machinery needed to make sphingolipids in Toxoplasma (and in other apicomplexans) is very unusual may eventually allow the development of new drugs against these organisms.