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SUMMARY:CANCELLED: Unravelling the whipworm niche at the host intestinal e
 pithelia - Dr Maria Duque-Correa - Wellcome-MRC Cambridge Stem Cell Instit
 ute - UoC
DTSTART:20231122T140000Z
DTEND:20231122T150000Z
UID:TALK207313@talks.cam.ac.uk
CONTACT:Anna Protasio
DESCRIPTION:Whipworms (_Trichuris spp_)  infect hundreds of millions of pe
 ople causing trichuriasis\, a major neglected disease. Whipworms are large
  metazoan parasites that inhabit a multi-intracellular niche within their 
 host caecal epithelia\, where they manipulate mucosal physiology and infla
 mmation through interactions with the intestinal epithelial cells and stem
  cell niche. These interactions enable chronic infections where whipworms 
 are tolerated for years\; but at a mechanistic level\, how they operate is
  not understood. My research aims to define these interactions and bring a
  mechanistic understanding to how they underpin whipworm invasion\, coloni
 sation\, and persistence in their mucosal niche. To address this aim\, my 
 lab employs a combination of in vivo and in vitro (using caecaloids) model
 s of _Trichuris muris_ infection and imaging and transcriptomic analysis. 
 Using these models\, we have shown that _T. muris_ first-stage (L1) larvae
  degrade mucus layers to access epithelial cells. In early syncytial tunne
 ls\, larvae are completely intracellular\, woven through multiple live div
 iding cells. Moreover\, using single-cell RNA sequencing of infected mouse
  caecum\, we revealed that progression of infection results in cell damage
  and an expansion of enterocytes expressing of Isg15\, potentially instiga
 ting the host immune response to the whipworm and tissue repair. Excitingl
 y\, we have now maintained whipworm-infected caecaloids for 24 days and ha
 ve observed growth and moulting of whipworms up to the L4 stage at times a
 fter infection similar to those _in vivo_. These results suggest whipworm-
 infected caecaloids can successfully support the in vitro life cycle _T. m
 uris_\, opening new opportunities to study host intestinal epithelial inte
 ractions with whipworms through infection\, while reducing the number of a
 nimals required for these studies. Collectively\, our research will unrave
 l intestinal epithelium invasion by whipworms and reveal specific host-par
 asite interactions that allow the whipworm to establish and persist in its
  multi-intracellular niche
LOCATION:Seminar Room\, Tennis Court Road\, Dept of Pathology.
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