Development of a synchrony model in Toxoplasma.  Replication of apicomplexan parasites is unusual and extremely variable with respect to biotic potential—in a single infection from 2 to 100,000 parasites may be produced.  This suggests cell cycle mechansims are novel in these parasites which in turn may provide new drug targets.  Together with the Roos lab, we have developed a set of tools for the study of Toxoplasma cell cycle that includes nuclear, cytoplasmic, and organeller markers that may be viewed in real time and a method to achieve synchronous parasite growth.  Turning to methods of the past, we generated transgenic parasites that express thymidine kinase (herpes simplex) and used a classical strategy of thymidine inhibition and release to establish synchronous growth through more than one division cycle (Radke and White, 1998).  As a tangent to this work, we found endogenous levels of thymidine in mice are sufficient to slow the growth TK+-RH parasites and as a result completely attenuated the potent virulence of this strain.  This data lends support the view that growth rate is a major virulent determinant in this parasite (Radke and White, 1999).