Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium

Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium

Project details

Cryptosporidium is a single celled eukaryotic parasite that resides in the cells of the small intestine and is the second leading cause of severe childhood diarrhea and crippling levels of morbidity and mortality in developing nations. Indeed, cryptosporidiosis is now considered one of the biggest killers of children <5 in Africa and SE Asia and has no effective treatments. Poor immunity against Cryptosporidium and recurrent infections mean that cryptosporidiosis is a key contributor to the vicious cycle of poverty and infection, which keeps developing nations from prospering.  

It is our goal to understand how Cryptosporidium recognizes and invades host cells, which is absolutely required for parasite survival. Whilst we understand in some detail how related Toxoplasma and malaria parasites invade their cognate cells nothing is understood about this process in Cryptosporidium nor if this process can be blocked to develop the first vaccine or drugs to clear infection. It is only now the field has the experimental tools to dissect invasion in Cryptosporidium whilst the Institute has also novel capabilities to understand this process.

This project will utilise molecular genetics to epitope tag and make knockouts of candidate parasite adhesins and dissect their role in invasion. New experimental techniques will also be used to determine the function of key proteins on the surface of Cryptosporidium and how they interact with host cells. Furthermore, this project will determine whether invasion can be targeted by antibodies to prevent infection, thus paving the way to developing the first vaccine against this insidious and deadly parasite.

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 utilise 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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