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Laser Analytics Group

 

'In Situ Cytometry Studies of the Endogenous Nano-chaperone Pathway for Gut Immune Cell Surveillance'

Jonathan Powell (Head of Biomineral Research and Fellow of Hughes Hughes ) and John Wills (Herchel Smith Fellow and Fellow of Girton College)

 

In 2015 we reported on our discovery of an endogenous nanomineral that chaperones luminal antigen and bacterial MAMPs to intestinal immune cells, as a part of normal immunosurveillance (Nature Nanotechnology. 2015 Apr;10(4):361-9). We have since shown that this pathway is promiscuous, across species and operates far beyond the ileal lymphoid patches as we originally described it. We have also shown that in humans there is hijack of the pathway by engineered food additive and excipient nanoparticles, to which humans are so commonly orally exposed. The recipient immune cells for both the endogenous and exogenous nanoparticles normally express the immuno-modulatory receptor PD-L1, but we showed that this fails in Crohn’s disease (Sci Rep. 2016 May 26;6:26747). These and ensuing studies face marked technical challenges: the endogenous chaperone is friable and labile and destroyed by processing so in situ analyses of frozen or anhydrous tissues is required. Signals- such as cytokines and chemokines that diffuse from cells- provide strong clues as to whether recipient cells of particles are initiating cell-cell signalling so gradients must be established, again in situ and quantitatively. Quantitative cell content with precise locational data and nearest neighbour phenotypes are also required. All of these- and more- are addressed by our development of in situ cytometry (ISC). Like similar quantitative histology and histochemistry techniques, ISC utilises open source software to segment cells and analyse their content and location simultaneously. Through integration of carefully controlled sample preparation, imaging, image analysis and machine learning, we are able to provide fully quantitative cell-by-cell outputs for the complex tissue types and variable tissue regions that make up the gastrointestinal tract, and demonstrate detailed nanoparticle interactions in situ.  

Date: 
Tuesday, 10 July, 2018 - 12:30 to 14:00
Contact name: 
Karen Scrivener
Contact email: 
Contact phone: 
+44 (0)1223 761208
Event location: 
Lecture Room 3, Department of Chemical Engineering & Biotechnology