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SUMMARY:Breaking the barrier: CSF-producing choroid plexus organoids model
  pathogen and drug entry to the brain   - Laura Pellegrini (LMB\, Cambridg
 e)
DTSTART:20220207T143000Z
DTEND:20220207T153000Z
UID:TALK168986@talks.cam.ac.uk
CONTACT:Elena Scarpa
DESCRIPTION:The choroid plexus (ChP) is a highly conserved and surprisingl
 y understudied secretory tissue in the brain. This tissue displays a numbe
 r of important functions in the brain such as forming a protective epithel
 ial barrier and secreting the cerebrospinal fluid (CSF). The CSF is import
 ant for the maintenance of physiological levels of nutrients in the brain\
 , for the transport of signalling molecules and growth factors and for its
  protective role in the regulation of intracranial pressure. To explore th
 e role of the ChP-CSF system\, we recently established a protocol to gener
 ate ChP organoids using a combination of signalling molecules that are phy
 siologically present during the stages of development of this tissue. More
  interestingly\, not only do these organoids develop the ChP but they also
  recapitulate fundamental functions of this tissue\, namely secretion and 
 formation of a tight epithelial barrier. Combining single-cell RNA-sequenc
 ing with immunohistochemical and EM validation\, we detected the presence 
 of ChP specific channels and transporters localised on the apical brush bo
 rder of the ChP epithelium. By testing different compounds\, we were able 
 to demonstrate the selective permeability of the ChP barrier in vitro\, us
 ing NMR. In addition\, we noticed the formation of large fluid-filled cyst
 s protruding from the organoids\, the contents of which\, analysed by mass
  spectrometry\, highly resembles human CSF. Finally\, we used this model t
 o test pathogen entry in the brain and we infected the organoids with live
  SARS-CoV-2. We found that SARS-CoV-2 infects ChP epithelial cells causing
  damage of this key brain barrier. In conclusion\, we believe this system 
 represents an excellent tool to study pathogen and drug entry in the brain
 . 
LOCATION:Online
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