IDENTIFICATION OF DIFFERENTIATION MUTANTS IN TOXOPLASMA GONDII

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The human pathogen Toxoplasma gondii is one of the most widely distributed protozoan parasites infecting approximately one-third of the world's population. T. gondii has achieved notoriety as a cause of life-threatening opportunistic disease in immunocompromised individuals. Asexual replication of T. gondii in humans and intermediate hosts is characterized by two forms: rapidly growing 'tachyzoites' and latent 'bradyzoite' tissue cysts both of which are essential for disease propagation and causation. Tachyzoites are responsible for acute illness and congenital neurological birth defects, while the more slowly dividing bradyzoite can remain latent within tissues life-long, presenting a continual threat to immunocompromised patients. The interconversion process between tachyzoites and bradyzoites is central to the parasite's survival and pathogenicity, yet it remains poorly understood at the genetic level. To this end we have recently developed a genetic screen to identify regulatory genes that control parasite differentiation and have isolated mutants that fail to convert to bradyzoites under differentiation conditions. Recently we have successfully scaled up the production of mutants and here we propose to characterize these mutants and use them to define genetic pathways that regulate bradyzoite differentiation and to isolate essential genes involved in this process.