Interaction with Toxoplasma parasites and the brain

Interaction with Toxoplasma parasites and the brain

Project details

Manipulation of host cells by intracellular pathogens is critical for their survival. Here pathogens inject their own proteins (called effectors) into the host cell and interfere with cell death and immune pathways to ensure their survival in the face of these human defence mechanisms. Pathogen effectors and mechanisms used to export these proteins into the host cell are thus critical for disease, whilst also representing a fascinating glimpse into how two organisms interact.

We are interested in identifying mechanisms of neuron manipulation by the brain-dwelling parasite Toxoplasma – the causative agent of blindness, congenital birth defects and disease in immunocompromised. Further, Toxoplasma has been linked to neuropsychiatric diseases suggesting that Toxoplasma may manipulate infected neurons to elicit behavioral changes. This project will use powerful molecular genetics available in Toxoplasma in combination with an infection model where cells report infection by expressing GFP. This project aims to identify effectors and characterize their role during infection and behavioral changes.

About our research group

The Tonkin laboratory is interested in understanding how human parasites interact with their host cell and how this can be exploited for developing new therapies. We work on both Toxoplasma, the causative agent of toxoplasmosis as well as Cryptosporidium the cause of severe diarrhea, which leads to enormous mortality and morbidity in developing nations. Latent Toxoplasma has no effective treatments putting patients at risk. Cryptosporidium on the other hand has no efficacious therapies leading to no treatment options. This is particularly dangerous in young children with no previous immunity.

Our lab uses molecular genetics and cell biological techniques to understand the interaction between Toxoplasma and Cryptosporidium and their respective host cells. This includes using CRISPR/Cas9 genetic screens, conditional knockouts, super resolution and live cell imaging modalities. We utilize and generate new technologies to most effectively understand host-pathogens interactions.

Our work has generated live attenuated strains for vaccination purposes and has collaborations with pharma to develop the first generation of drugs to target these insidious and ubiquitous parasites.

 

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