Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is a disease that can be found on every continent. There are two distinct phases of the disease, the acute phase which forms tachyzoites and the latent phase which forms bradyzoites. In a healthy person the disease starts off in the acute phase and the immune system will respond, placing pressure on the parasite to convert to the latent stage. In this stage the parasites form cysts containing bradyzoites in the brain and other organs, where they will persist for a life-long and untreatable infection. Approximately 80 million people in the United States are infected with the chronic form. T. gondii can convert bradyzoites to tachyzoites which can quickly proliferate once the infected person becomes immunocompromised, leading to encephalitis and heart failure.
Many factors that regulate the conversion between the acute and chronic have yet to be identified but epigenetic regulators appear to play a critical role. Bromodomain proteins bind acetyl-lysine residues on histone tails and link acetylated histones to the protein complexes that regulate transcription. There are 12 bromodomain proteins in Toxoplasma, six of which are parasite specific. We have identified T. gondii bromodomain protein 5 (TgBDP5) that is specific to coccidia parasites and likely to regulate a parasite-specific pathway, such as differentiation between acute and chronic disease.
Our goal is to determine the contribution of TgBDP5 to parasite gene expression. First, to determine the impact of TgBDP5 on T. gondii viability, I generated a knockout strain and am currently identifying the impact the loss has on growth. We will also determine the functional TgBDP5 complex and their target genes. Using ChIP-seq and transcriptomics, I will discern the genes regulated by TgBDP5 throughout the stages, this will determine TgBDP5’s role in epigenetic gene regulation during both replication and differentiation between acute and chronic stages.
