The Sheiner Group
We study Toxoplasma not only as an example of a divergent eukaryote, but also as a model for the phylum Apicomplexa, which includes parasites of human and veterinary medical importance like Plasmodium spp that cause malaria. In addition to expanding the repertoire of explored biological systems we hope to pinpoint new parasite-specific structures and feature that are potential targets for intervention.
Our lab is focused on divergent pathways in the function and biogenesis pathways of the T. gondii organelles of endosymbiotic origin – the apicoplast and the mitochondrion.
Mitochondria and mitochondria-like organelles are essential for most eukaryotes including apicomplexan parasites. The apicomplexan mitochondrion shows several divergent features compared to well-studied systems such as plants, fungi and metazoans: these parasites have a single large mitochondrion per cell that only divides simultaneously with cytokinesis unlike mammalian mitochondria that may change their numbers independently of the cell cycle; Apicomplexans have the smallest known mitochondrial genome encoding only three open reading frames, one of which is the target of the antimalarial atovaquone. Sequence analysis and a series of indirect studies also suggest divergent features of major components of the mitochondrial electron transport chain including the mitochondrial ATP synthase, and point to divergence also in pathways such as mitochondrial tRNA import and in mitochondrial-ribosome functions. Out lab studied the mechanistic details of some of those pathways, where knowledge of the molecular players and their mode of action may inform new drug design.
The apicomplexa ancestor engaged in secondary endosymbiosis, thus acquiring a plastid of red algal origin, with a complex four-membrane architecture. Apicomplexan then have gone through further “life-changing” events, losing the ability to perform photosynthesis and turning to parasitism. While no longer photosynthetic the apicoplast hosts essential metabolic pathways. Both metabolic and housekeeping pathways hosted in the apicoplast stroma are known targets for anti-apicomplexan drugs. However, less attention was focused on the pathways hosted in the peripheral compartments. We explore what proteins and pathways are hosted in these compartments and characterize their roles and molecular mechanisms.
Research Group Members
Hamza Ali Abd Elati, PhD Student
Daniel Walsh, PhD Student
Saniya Crouch, PhD Student