MRC DTP in Precision Medicine

Spatially and temporally resolving blood fluke pathogenesis

Supervisors

Professor Matt Berriman, School of Infection and Immunity, University of Glasgow 

Professor Andrew MacDonald, Institute of Immunology and Infection Research, University of Edinburgh 

Professor Thomas Otto, School of Infection and Immunity, University of Glasgow 

Summary

Schistosomiasis is an acute and long-term chronic neglected tropical disease, caused by infections with schistosomes (blood flukes). The parasites develop in humans over a period of several weeks, before becoming adult worms that form breeding and pairs that live for years in blood vessels of the gut or bladder, depending on infective species. Mating worms produce hundreds of eggs per day, which exit the body to enable transmission, or transit around the body (especially to the liver), causing much of the disease pathology.  

Disease progression is hugely variable, but its largely driven by the immune system reacting to eggs, to form granulomas composed of multiple immune cell types. Granulomas differ between tissues, with the liver particularly badly affected. Eggs are multicellular, express different genes depending on their context and play an active role in the progression of granuloma development.  In contrast to other parts of the parasite, almost nothing is known about how single cells vary across the egg and over time.   

This project will investigate how eggs interact with host tissues, during the formation and maturation of granulomas in murine infections. Gene expression changes will be interrogated from individual host and egg cells across different infected tissues, at different infection intensities. By integrating immune readouts with a spatio-temporal understanding of cellular transcriptomic changes, we will transform our understanding of granuloma formation and reveal novel biomarkers for better management of disease progression.