The infectious agent Toxoplasma gondii is a member of the phylum Apicomplexa, which includes the organisms responsible for malaria and coccidiosis. Although most T. gondii infections are asymptomatic, they can lead to severe disease and even death in utero and in individuals immunocompromised by AIDS or cancer. The devastating effects of a Toxoplasma infection are a direct consequence of its lytic cycle, which consists of attachment to the host cell invasion, intracellular replication and egress. Both invasion and egress involve fluctuation in intracellular [Ca], morphological changes and secretion from various organelles. The process of egress is often lethal to the cell but little is known about this process at the genetic or molecular lever. The goal of this proposal is to identify and characterize genes that play critical roles during egress. Mutations that affect egress can be isolated since this process can be induced by calcium ionophore and affecting genes involved in ionophore-induced egress (HE might not necessarily be lethal to the parasite. Two distinct genetic screens will be performed to isolate TIE mutants. The study of these mutants and the genes affected will help us characterize the steps involved in ionophore-induced and normal egress and identify the signals that induct the parasite to exit the host cell.
