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SUMMARY:When parasitology meets cell biology: Mechanistic insights into th
 e functional biology of schistosomes.  - Prof Tony Walker (Kingston Univer
 sity London)
DTSTART;VALUE=DATE-TIME:20260223T133000Z
DTEND;VALUE=DATE-TIME:20260223T143000Z
UID:https://talks.ox.ac.uk/talks/id/83784739-3495-473d-a0ee-43e90935cb0d/
DESCRIPTION:affecting over 230 million people worldwide across 68 developi
 ng countries. This seminar will focus on two areas of our research on Schi
 stosoma mansoni that open new possibilities for the development of novel a
 nti-schistosome therapeutics: (i) the unravelling of heat shock protein 90
  (HSP90) as a vital signalling hub in the parasite\; and (ii) the developm
 ent of a novel in vitro stem-cell focused drug screening platform using th
 e developing liver schistosomula stage.\n HSP90s are molecular chaperones 
 often produced by cells in response to hostile conditions. We discovered t
 hat HSP90 was upregulated in the developing schistosomula\, and phenotype 
 assays revealed that various HSP90 inhibitors profoundly attenuated parasi
 te 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 ova
 ries of adult worms was blocked. SiRNA-mediated knockdown of the cytoplasm
 ic HSP90 alpha isoform 2 (Smp_072330) also attenuated stem cell proliferat
 ion and restricted schistosomulum growth\, supporting the importance of th
 is 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. \nBuilding on our
  interest in schistosome stem cell biology we aimed to develop a novel dru
 g 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 supres
 sed stem cell proliferation by at least 75%. Sixteen ‘hit’ compounds f
 rom the primary screen were prioritised for further testing/confirmation w
 ith testing done in both simple and complex media. Six compounds were fina
 lly selected for further investigation\, all of which killed developing sc
 histosomula and abolished both somatic and germinal stem proliferation in 
 adult male and female worms. In addition to identifying a panel of new ant
 i-schistosomal compounds with associated predicted targets\, the findings 
 provide mechanistic insights into the somatic stem cell biology of schisto
 somes. \nBio Sketch:\nTony Walker is Professor of Cell Biology in the Scho
 ol of Life Sciences\, Pharmacy and Chemistry at Kingston University (KU) L
 ondon. Since starting at KU over two decades ago\, his research has aimed 
 to better understand the basic biology of schistosome parasites and how th
 ey interact with their mammalian and snail hosts. Using techniques such as
  protein kinase assay\, immunohistochemistry\, confocal laser scanning mic
 roscopy\, RNA interference\, and phenotype assays\, his research seeks to 
 define the fundamental mechanisms by which cellular proteins regulate schi
 stosome 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.\n
 \nSpeakers:\nProf Tony Walker (Kingston University London)
LOCATION:Seminar rooms 7 & 8\, Life and Mind Building\, South Parks Road\,
  OX1 3EL
TZID:Europe/London
URL:https://talks.ox.ac.uk/talks/id/83784739-3495-473d-a0ee-43e90935cb0d/
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DESCRIPTION:Talk:When parasitology meets cell biology: Mechanistic insight
 s into the functional biology of schistosomes.  - Prof Tony Walker (Kingst
 on University London)
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