Exploring the function of a novel tyrosine kinase like (TKL) protein in Toxoplasma endodyogeny

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PROJECT SUMMARY/ABSTRACT Toxoplasma gondii is an important human pathogen that divides by a unique mode of cell division called endodyogeny that is quite distinct from binary fission that occurs in mammalian cells. Since Toxoplasma division is divergent from higher eukaryotes, a better understanding of this complex process and identification of its key components and their mode of regulation would potentially open doors for selective strategies to disrupt infection. TgTKL4 is a member of tyrosine kinase like (TKL) family protein in Toxoplasma that localizes to parasite cytoplasm with its expression mainly confined to synthesis (S), mitosis/cytokinesis (M/C) phases of the cell cycle. Interestingly, loss of this kinase causes defects in cell division that results in misshapen parasites with compromised fitness and attenuated virulence. Specifically, TgTKL4 null mutants with abnormal morphology display significant defects in in vitro propagation suggesting loss of this kinase affects one or more stages of Toxoplasma lytic cycle. Since TgTKL4 is a cell-cycle regulated kinase and parasites deficient in this enzyme show abnormal shape, we hypothesize that this kinase is a part of the signaling network that dictates parasite morphology during endodyogeny. To further understand the role of this novel TKL kinase in parasite replication, we propose to: (1) Identify substrates of TgTKL4; and (2) Determine the role of TgTKL4 in Toxoplasma endodyogeny. Thus, our proposed work will help us understand the precise function of TgTKL4 and signaling network associated with this kinase during cell division that determines parasite morphology.