Developing a novel drug screening platform for schistosomes using the free-living flatworm Schmidtea mediterranea

Schistosoma mansoni is one of three major schistosome species that infect over 240 million people across 70 developing countries, with an additional 0.6 billion at risk of infection. These blood-dwelling parasites cause human schistosomiasis by producing countless eggs intended for transmission via snail intermediate hosts. However, these eggs often become trapped in vital organs, like the human liver, causing damage through tissue inflammation. Adult schistosomes have a lifespan of 3–5 years but can endure for up to two decades in the blood vessels, leading to significant morbidity and mortality in endemic regions.  

Control measures rely heavily on mass drug administration of praziquantel, the sole drug for widespread schistosomiasis treatment. Unfortunately, schistosomes can become refractory to this drug, and treatment does not prevent re-infection. This project aims to shed light on schistosome stem cell biology, growth, and development, and explore innovative strategies for schistosomiasis control through the development of novel drug-targeting approaches.  

Planarians, close relatives of schistosomes, are free-living flatworms with remarkable regenerative capacities and abundant pluripotent stem cells. This makes them an ideal model for studying the mechanisms that underpin stem cell proliferation in flatworms in general, including in schistosomes.  Planarians are also easy to maintain in the laboratory. This project will initially focus on creating a novel platform for drug screening in the planarian, Schmidtea mediterranea; the data generated will then be interrogated to identify S. mansoni stem cell targets for study and drug prioritisation work.  

We will begin by utilising planarian tissue fragments/biopsies that contain a significant number of proliferating stem cells. Our initial goal is to demonstrate that these biopsies exhibit characteristics like those observed in the stem cells in actively growing and developing S. mansoni worms. We will then investigate the cellular events that underpin tissue regeneration of planarians from the biopsies to provide valuable insights into the molecular processes, including through cellular signalling, occurring in planarians during development. We will perform drug screens of planarian tissue regeneration to inform our selection of targets in S. mansoni. In addition to the experimental work, this project will also entail extensive planarian and schistosome bioinformatics analysis.  

We invite talented and motivated researchers interested in cell biology to join us. This project offers comprehensive training in molecular parasitology, encompassing various approaches including bioinformatics, proteomic-based techniques, confocal laser scanning microscopy, drug assay development, phenotype assays, and stem cell staining.  

Applicants should have achieved at least an Upper Second (2i) class degree in a related subject (e.g. Biochemistry, Genetics, Biological Sciences). Experience in laboratory work or an MSc/MSc By Research would be an advantage.