The protozoan parasite Toxoplasma gondii causes the disease toxoplasmosis that chronically infects over a third of the world’s population. The current drugs that are available to treat toxoplasmosis are unsuitable for vulnerable patients due to toxic and allergic reactions and there is no available treatment that can clear the chronic infection. Therefore, it is of great importance to develop safer, more effective therapies for the treatment of toxoplasmosis.
Lysine acetylation is an essential process in the parasite, regulating multiple cellular pathways such as gene expression, metabolism and parasite differentiation. The bromodomain (BRD) proteins are a vital component of lysine acetylation dynamics, recognizing and binding acetylated lysine residues and modulating protein-protein interactions to elicit a downstream response. Preliminary data indicates that a compound that inhibits BRD function selectively inhibits Toxoplasma proliferation, implying that BRD proteins are attractive targets for drug development.
This proposal seeks to examine the functions of two unstudied BRDs in Toxoplasma. Biochemical and molecular approaches will be utilized to determine the subcellular localization of each BRD, their associated factors and the subset of gene loci where the BRDs associate. Ultimately, this approach will identify the BRD that is most suitable for advancing to drug development. These efforts will also provide novel insight into the function of these unstudied proteins and will yield a trove of hypothesis-generating data that can be used to obtain additional funding from external sources to further delve into BRD biology in the Toxoplasma parasite.
