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TATA-Binding Protein 1 is Essential for Intracellular Infection by the Protozoan Parasite Toxoplasma gondii
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Toxoplasma gondii is an intracellular protozoan parasite that causes the disease toxoplasmosis, which infects approximately thirty to fifty percent of the world’s population. Treatments for toxoplasmosis are lacking and immunocompromised individuals are at risk of a reactivation of acute infection. Studying gene expression in Toxoplasma can provide insight on potential antiparasitic drug targets to combat toxoplasmosis. TATA-binding proteins (TBP) are found in most eukaryotic organisms and play a vital role in initiating gene expression. Presently, little is known about the role and function of the two TBP’s in Toxoplasma, TgTBP1 and TgTBP2. We hypothesize that TgTBP1 plays an essential role in transcriptional regulation and it critical for parasite viability. To test this, we generated a transgenic parasite line to knockdown tgtbp1 by replacing its promoter with a tetracycline-regulatable promoter. We confirmed integration of the tetracycline-regulatable promoter at the tgtbp1 genomic locus and show a decrease in tgtbp1 expression upon addition of anhydrotetracycline (ATc), a derivative of tetracycline. We performed parasite phenotyping assays upon TgTBP1 knockdown to determine its effect on parasite growth and replication. Knockdown of tgtbp1 is lethal to parasites, and parasite replication is slowed down compared to wild-type parasites. Our findings provide important considerations for targeting transcription initiation with therapeutic drugs to treat toxoplasmosis.
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Event Graduate Research Conference
Department Genetics (GRC)
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Added April 5, 2022, 2 p.m.
Updated April 5, 2022, 2 p.m.
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