The Gaji Lab @ VT

Protein kinases are involved in regulating many important biological events in a cell through phosphorylation and have been exploited as drug targets in many disease contexts. In Toxoplasma also, kinases have been shown to play a key role in parasite motility, invasion, replication, egress and also survival within the host by nullifying host defense factors. An interesting set of kinases present in Toxoplasma genome are proteins that belong to Tyrosine Kinase Like (TKL) family and our long-term goal is to define the role of these kinases in Toxoplasma biology.

 

Bioinformatics analysis of Toxoplasma genome revealed that there are eight genes that are annotated as TKLs and six of these have been classified as being important for parasite growth in vitro. We have named the TKLs important for parasite growth numerically according to their predicted fitness scores and endogenously tagged them with an epitope tag to determine their localization in the parasite. Interestingly, these kinases localize to various compartments in the parasite including the nucleus, cytosol, IMC and Golgi.

 

Since many of these TKL kinases have been predicted to be important for parasite fitness, we hypothesize that these proteins play critical roles in parasite propagation in vitro and pathogenesis in vivo. Hence, we would like to address the following questions towards characterization of these proteins in Toxoplasma biology.

 

1. What is the precise role of these proteins in the lytic cycle of Toxoplasma?

2. What is the signaling network each of these kinases are involved in?

3. What is the role of these proteins in acute and chronic toxoplasmosis?