The overall objective of this core, is to test the activity of new agents that can be used for the treatment of Toxoplasma gondii in animal (mouse) models in a rapid manner. Potential drugs which have been identified by the supporting projects to have activity against T. gondii in in vitro tissue culture systems or appear to have potent activity against a potential target (e.g. dihydrofolate reductase, nucleoside transport, ribosome function, cyclophilin, HGPRT, etc.) will then be tested in animal models of infection. In addition, knockout mutants generated by the projects or other cores will be tested for virulence and ability to form tissue cysts. Prior to animal testing, all compounds will be tested in vitro in the Core Director's laboratory in order to ascertain the magnitude and rate of activity of the various compounds. This may have an important impact on the appropriate design of the animal tests. However, we are aware that there may be important discordance between in vivo and in vitro results, and that activity against a particular enzyme or organelle may be a better predictor of activity in animal models. The animal and in vitro models that have been chosen are those which have been used commonly by the Core Director in his laboratory over the last fourteen years and are the models which have been used as the standard to determine whether therapeutic agents warrant further testing in humans for anti-Toxoplasma activity. A major emphasis of this facility will be to perform these assay in a rapid manner in order to be a part of the ongoing development of new anti-Toxoplasma compounds.
