Biosciences Research Seminar - An epithelial damage sensor system decoded; the first intracellular signal of your life?

Part of the Biosciences lunchtime research seminar series

A Biosciences seminar
Date25 November 2021
Time12:30 to 13:30
PlaceEvent held via Microsoft Teams

Speaker: Assistant Professor Tom Carney, Lee Kong Chian School of Medicine, Nanyang Technological University. Host: Dr Steffen Scholpp

Tom Carney graduated from the Genetics Department at the University of Adelaide before embarking on a PhD in zebrafish developmental biology in the laboratory of Robert Kelsh at the University of Bath, UK, studying specification of neural crest derivatives. He continued zebrafish research as a postdoctoral fellow at the Max Planck Institute for Immunobiology in Freiburg, Germany from 2004. Here he analysed a number of epidermal mutants, elucidating the role of novel extracellular matrix proteins and serine proteases in development. He took up an assistant Principal Investigator position in IMCB in October 2008, and then became a joint Assistant Professor at the Lee Kong Chian School of Medicine at NTU in 2014. His current research focuses on dermal and epidermal pathways in development and modelling human disease states in zebrafish.


Abstract

Almost all stratified epithelia exist in a state of balance, continually turned-over and replaced from a basal stem cell compartment. In addition, most are poised to respond rapidly to external insults or re-establish the barrier upon wounding. The mechanisms maintaining this poised state must permit an immediate, yet robust response.

We have identified a protease and inhibitor system, present in the basal keratinocytes of vertebrates, essential to maintain both epithelial integrity and quiescent inflammation in zebrafish. Upon loss of the inhibitor (or mis-expression of its cognate protease target), keratinocyte stem cells attain a striking migratory phenotype and the epidermis becomes inflamed, hallmarks of a wound response.

The target of this protease is shown to be a protease activated receptor (PAR2), and we have determined the cellular events resulting from dysregulation of this system, including a marked increase in Reactive Oxygen Species, which, along with activation of other critical pathways, initiates inflammation. Intriguingly, the epithelial defects are uncoupled from the inflammatory responses, and we have implicated the MAPK pathway and intracellular lipid signalling in the keratinocyte phenotype.

Finally, we have found an earlier role for PAR2 in zygote activation following fertilisation, highlighting that this system has been deployed in multiple contexts in development and tissue repair.

Attachments
Seminar_Series_Poster_25112021.pdf (486K)

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