Let me in! How Toxoplasma invades human cells

Let me in! How Toxoplasma invades human cells

Project details

Toxoplasma, like all apicomplexan parasites (including malaria), must invade host cells and move through tissue for survival in the human host. Invasion and parasite motility are powered by an actomyosin-based molecular ‘motor’, which is critical for survival in the host.

We are characterising components of the ‘glideosome’ to understand their importance during pathogenesis. We recently identified some novel components that link this motor to parasite ligands, and may be potential drug targets for treating toxoplasmosis and malaria.

This project aims to characterise the role of these proteins in Toxoplasma tissue dissemination and host cell invasion. Students will use molecular genetic, imaging and other cellular techniques to understand the role that these molecules play in parasite virulence.

About our research group 

The phylum Apicomplexa comprises a group of parasites that must invade host cells for survival and proliferation. The Tonkin lab is interested in understanding the molecular mechanisms that allow these pathogens to invade target host cells and then extensively modify these for their own advantage.

We primarily work on Toxoplasma and Plasmodium spp. Plasmodium spp cause malaria and Toxoplasma is responsible for congenital birth defects, blindness and disease in immunocompromised individuals. Toxoplasma is highly experimentally tractable and acts as an important model for understanding the genetics and cell biology of infecition in Plasmodium spp and other apicomplexan parasites. We employ cross-disciplinary approaches to understanding parasite virulence mechanisms including molecular genetics, quantitative proteomics, cell biology and molecular biology.  

Monitoring the importance of Ca2+ signaling during Toxoplasma host cell invasion using live cell imaging: Toxoplasma parasites were engineered to express the Ca2+ biosensor GCaMP (as well as mCherry fluorescent protein). During extracellular motility Toxoplasma has high levels of cytosolic Ca2+ (high green fluorescence), but after host cell invasion (arrow) levels of Ca2+ rapidly drop (low green fluorescence).

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