Our research
We study the single celled parasite Toxoplasma gondii, which is fascinating for many reasons:
it is a hugely prevalent parasite, thought to have infected up to 1/3 of the global human population ( we call this highly successful…)
it also infects a broad range of animals and birds
it survives inside host cells and uses an array of secreted proteins to interact with the host, inhibiting immune responses and scavenging nutrients (and much more)
it sets up longterm infections forming semi-dormant cysts in the brain, eyes, skeletal muscle and myocardium.
Many of our projects focus on the cyst stage of Toxoplasma, where the parasites differentiate into the slow-growing bradyzoite.
Some our research questions….
How do secreted proteins facilitate chronic infection?
Can detailed quantification help us discover more from in vitro cysts?
How is the PV remodelled to form the cyst?
How is the formation and growth of the cyst wall regulated?
Do the secreted proteins expressed by bradyzoites promote parasite survival in specific cell types?
Our approaches
CRISPR screening
We use CRISPR/Cas9 to generate Toxoplasma mutants with specific genes disrupted. By doing this in a mixed pool, we can find out which genes are important for the phenotype we are investigating.
Imaging
There is nothing we like more than seeing our beautiful parasites!
We have combined this love with developing new tools and have developed a protocol for Expansion microscopy of the Toxoplasma cyst. We are also working on automating quantification of the number of parasites within this packed structure.
In vitro models
Longterm Toxoplasma cysts are formed predominantly in the central nervous system and skeletal muscle. Cysts are also formed in vitro in tissue culture. This can be induced by stressing the parasites but occurs spontaneously in certain cell types, including myotubes and neurons. We believe there is a lot of biology to learn from in vitro cysts, especially in studying their formation. We combine in vitro cysts with high throughput imaging and genetic screening.
Through a collaboration with the Blume lab we (Elena!) have set up myotube culture and look forward to getting started on neurons soon…
