WEHI PhD Completion Seminar hosted by Associate Professor Chris Tonkin

Abdulrahman Alammar
PhD Student – Tonkin Laboratory, Infection and Global Health division, WEHI

Dissecting the function of thrombospondin repeat-containing proteins in the diarrhoeal pathogen Cryptosporidium

Davis Auditorium

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Including Q&A session

Cryptosporidium is a major cause of diarrhoeal disease in young children and immunocompromised patients. How Cryptosporidium attaches to, invades, and establishes infection within the host enterocyte — remain poorly understood. The C. parvum genome encodes twelve thrombospondin repeat-containing proteins (CpTSPs), predicted to act at the host–parasite interface, but their function is not understood. 

In this project, the function of prioritised subset of five CpTSPs were investigated. I used CRISPR-based reverse genetics, comparative phenotyping, ultrastructure expansion microscopy, and interaction proteomics to understand their function. CpTSP1, CpTSP3 and CpTSP10 could be tagged but not knocked out under the conditions tested, whereas CpTSP11 and CpTSP12 knockouts were recoverable but showed defects in virulence. TSP11 and 12 shared collar-like apical localisation. Immunoprecipitation and mass spec identified interacting proteins CpTSP11 functions during invasion as part of a larger complex. Together, this work establishes no-redundant roles for CpTSP family in the biology of Cryptosporidium, and furthermore, identifies CpTSP11 and CpTSP12 as likely being involved in host cell invasion. Collectively, these results provide some of the first molecular evidence into how Cryptosporidium infects its host to cause disease. 

All welcome!