Journal article

An integrative computational model for intestinal tissue renewal

IMM van Leeuwen, GR Mirams, A Walter, A Fletcher, P Murray, J Osborne, S Varma, SJ Young, J Cooper, B Doyle, J Pitt-Francis, L Momtahan, P Pathmanathan, JP Whiteley, SJ Chapman, DJ Gavaghan, OE Jensen, JR King, PK Maini, SL Waters Show all



OBJECTIVES: The luminal surface of the gut is lined with a monolayer of epithelial cells that acts as a nutrient absorptive engine and protective barrier. To maintain its integrity and functionality, the epithelium is renewed every few days. Theoretical models are powerful tools that can be used to test hypotheses concerning the regulation of this renewal process, to investigate how its dysfunction can lead to loss of homeostasis and neoplasia, and to identify potential therapeutic interventions. Here we propose a new multiscale model for crypt dynamics that links phenomena occurring at the subcellular, cellular and tissue levels of organisation. METHODS: At the subcellular level, determinis..

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University of Melbourne Researchers


Awarded by EPSRC

Awarded by National Cancer Institute

Awarded by Engineering and Physical Sciences Research Council


Funding Acknowledgements

The authors wish to thank Owen Sansom and Mohammad Ilyas for fruitful discussions on Wnt signalling and crypt dynamics and Eleanor Boston, Carina Edwards and Matthew Johnston for their participation in various Chaste programming sessions. We gratefully acknowledge the support provided by the EPSRC (GR/S72023/01 and EP/F011628). P.K.M. was partially supported by a Royal Society Wolfson Merit Award. P.M. and P.K.M. were partly supported by NIH Grant U56CA113004 from the National Cancer Institute. B.D. thanks Cancer Research UK for financial support. HMB and PKM were partially supported by PMI2 (British Council).