Our specific research questions include:
How do parasites physically divide by internal budding?
For signaling purposes, does mitosis complete before the onset of cytokinesis?
What is the function of the basal complex in mature parasites?
How do parasites secrete organelles in a calcium dependent fashion?
What genetic changes underlie lab-adaptation of parasites?
The protozoan parasite Toxoplasma gondii is a member of the phylum Apicomplexa and can cause severe disease in humans. This parasite is easily grown and manipulated in vitro and has in recent years developed as a safe and versatile model for other apicomplexan parasites (e.g. malaria). We are using and developing forward, reverse and functional genetic tools using enzymatic as well as fluorescent protein reporter assays in combination with cell sorting and fluorescence microscopy to learn more about the parasite’s cell biology.
Toxoplasma divides through a unique internal budding mechanism producing two daughters per division round. This is unusual for apicomplexan parasites, which typically have polyploid cells from which numerous daughters can be produced. However, the last round of S-phase and mitosis is typically linked to budding of daughters in all apicomplexan division strategies. Thus, Toxoplasma’s binary division is the simplest variation on this theme and is why we use it as a model. Our interests range from how mitosis works, how it is coordinated with cytokinesis, how the parasite cytoskeleton scaffolds are assembled, and how the parasites separate in the end to complete division.
Host Cell Invasion
Since no parasite replication takes place outside a host cell, successfully invading a host cell is critical to survival of the parasite. The asexual tachyzoite stages of Toxoplasma are able to invade any nucleated cell from any warm-blooded animal. This wide host range sets it apart from the typical apicomplexan parasite which has a narrow range (e.g. the malaria causing Plasmodium merozoites only invade erythrocytes from a single host). The basic mechanism of parasite-powered host cell invasion is largely conserved across Apicomplexa, but Toxoplasma’s wide host range and easy lab cultivation make it easily accessible model. Our current interest lies in identifying and understanding through which proteins Ca exerts its function in organelle secretion.