When parasitology meets cell biology: Mechanistic insights into the functional biology of schistosomes.
affecting over 230 million people worldwide across 68 developing countries. This seminar will focus on two areas of our research on Schistosoma mansoni that open new possibilities for the development of novel anti-schistosome therapeutics: (i) the unravelling of heat shock protein 90 (HSP90) as a vital signalling hub in the parasite; and (ii) the development of a novel in vitro stem-cell focused drug screening platform using the developing liver schistosomula stage.
HSP90s are molecular chaperones often produced by cells in response to hostile conditions. We discovered that HSP90 was upregulated in the developing schistosomula, and phenotype assays revealed that various HSP90 inhibitors profoundly attenuated parasite viability/development. In vitro liver-stage, ex-vivo adult male/female worms and eggs were also killed. Strikingly, stem cell proliferation in the skin, lung and liver schistosomula, and the testicular lobes and ovaries of adult worms was blocked. SiRNA-mediated knockdown of the cytoplasmic HSP90 alpha isoform 2 (Smp_072330) also attenuated stem cell proliferation and restricted schistosomulum growth, supporting the importance of this HSP90 isoform. Phosphorylation of schistosomula Akt/protein kinase B, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase were also modulated by inhibition, suggesting HSP90 regulates core ‘system-based’ signalling pathways in the parasite.
Building on our interest in schistosome stem cell biology we aimed to develop a novel drug screening platform employing non-synchronous in vitro grown liver-stage schistosomula with high-content quantitative analysis of dividing somatic neoblasts within the parasite to define phenotype. Drug screening employed a stem cell focused library containing 280 compounds, 44 of which supressed stem cell proliferation by at least 75%. Sixteen ‘hit’ compounds from the primary screen were prioritised for further testing/confirmation with testing done in both simple and complex media. Six compounds were finally selected for further investigation, all of which killed developing schistosomula and abolished both somatic and germinal stem proliferation in adult male and female worms. In addition to identifying a panel of new anti-schistosomal compounds with associated predicted targets, the findings provide mechanistic insights into the somatic stem cell biology of schistosomes.
Bio Sketch:
Tony Walker is Professor of Cell Biology in the School of Life Sciences, Pharmacy and Chemistry at Kingston University (KU) London. Since starting at KU over two decades ago, his research has aimed to better understand the basic biology of schistosome parasites and how they interact with their mammalian and snail hosts. Using techniques such as protein kinase assay, immunohistochemistry, confocal laser scanning microscopy, RNA interference, and phenotype assays, his research seeks to define the fundamental mechanisms by which cellular proteins regulate schistosome form and function. The research could result in the identification of candidate proteins for the development of novel anti-schistosome drugs to help control the neglected tropical disease, human schistosomiasis.
Date: 23 February 2026, 13:30
Venue: Seminar rooms 7 & 8, Life and Mind Building, South Parks Road, OX1 3EL
Speaker: Prof Tony Walker (Kingston University London)
Organising department: Department of Biology
Organiser contact email address: andrea.kastner@biology.ox.ac.uk
Host: Prof Gabriel Rinaldi (Department of Biology, University of Oxford)
Booking required?: Not required
Audience: Members of the University only
Editor: Andrea Kastner