Uncontrolled Toxoplasma growth is the primary mechanism by which the parasite causes severe and life-threatening disease. The parasite replicates by a process termed endodyogeny, where two daughter parasites form within a single mother. A key step in endodyogeny is formation of the daughter cell inner membrane complex, which is an unique organelle that lies directly underneath the plasma membrane and is required for parasite motility and replication. During daughter cell development, the nascent IMC emerges from a complex named the daughter cell scaffold (DCS). Despite its importance, the DCS is poorly characterized and few of its constituent proteins are known. Here, we hypothesize that the Toxoplasma F-box protein, TgFBXO1, is a critical component of the DCS. To test our hypothesis, we will determine: i) how TgFBXO1 is targeted to the DCS, ii) how TgFBXO1 regulates inner membrane complex development and organization, and iii) which TgFBXO1-interacting proteins are important for inner membrane complex development. Together, these studies will provide in depth mechanistic detail for a protein complex that is critical for growth of an important protozoan pathogen. Furthermore, they were serve as a springboard for future studies aimed at developing novel anti-parasitic drugs that function by targeting this complex.
Toxoplasma replication is the underlying mechanism by which this parasite causes severe and life-threatening disease. The work proposed here seeks to define how the parasite forms a structure called the inner membrane complex, which is analogous to its skeleton. Data from these studies will also identify novel drug targets.
