| Summary: | Toxoplasma gondii is an ubiquitous obligate intracellular protozoan parasite that causes permanent infections in 10-30% of humans worldwide. It plays a role as an opportunistic parasite in AIDS patients and can cause eye diseases. T. gondii has veterinary importance and has an important role in abortion and mortality in economic animals like sheep, goats and pigs in all parts of the world. It is also a major cause of foetal abortion in human and other mammals and is associated with some behavioural and neurological effects. Two metabolic enzymes; pantothenate synthase producing the precursor to Coenzyme A, required by 4% of enzymes in eukaryotic cells, and tyrosine-phenylalanine hydroxylase, able to produce tyrosine and L-DOPA, are the main subjects of my study. Co A biosynthesis is likely to be required for parasite growth, but the necessity of tyrosine hydroxylase for parasite growth is less obvious. This study will explain the current knowledge on these enzymes and attempt to evaluate their potential as novel drug targets against toxoplasmosis. Systems were developed to test potential pantothenate synthase and tyrosine hydroxylase inhibitors. The tyrosine hydroxylase is proposed to uniquely be secreted out of the parasite into the parasitophorous vacuole. The localisation of the enzyme is being examined by transgenic expression with a GFP tag. Further, the role of the enzyme in dopamine synthesis was investigated in PC12 cells, widely used as a model dopaminergic cells. A biological system is being developed for T. gondii parasite differentiation to bradyzoites whilst maintaining the capacity to express and secrete dopamine. The promising outcomes of these experiments will increase our knowledge of growth and metabolism in this important parasite and highlight new drug targets.
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