2012 Annual Report 1a.Objectives (from AD-416): Define molecular basis of toxoplasmosis. 1b.Approach (from AD-416): T. gondii strains of different genetic background will be isolated and cultured. 3.Progress Report: Toxoplasma gondii is a widespread parasite of animals that causes zoonotic infections in humans. Why some people infected with this parasite become sick while most remain asymptomatic is unknown. Recently, attention has been focused on the genetic differences among isolates of T. gondii from sick and healthy humans and animals. The virulence (disease causing capacity) of different strains has been studied in mice. We have used genetic crosses (by feeding two strains to cats, and then collecting oocysts-product of sexual cycle). Analysis of the progeny revealed that differences between the highly virulent type I strain and intermediate virulent type II are independent of the protein kinases found in rhpotries (gland like structures in the parasite called ROP18), but are due to allelic differences in another kinase called ROP5. To further understand the molecular basis of virulence in Toxoplasma, genetic crosses are now being made among different strains of T. gondii.