Award details

A multidisciplinary approach to studying crypt-villus homeostasis and regeneration in the intestinal epithelium

Reference	BBS/E/F/00042697
Principal Investigator / Supervisor	Dr Maria Pin Arias
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	123,463
Status	Completed
Type	Institute Project
Start date	06/01/2014
End date	28/02/2017
Duration	37 months

Abstract

We aim to study the mechanisms regulating the continuous renewal of the intestinal epithelium in physiological conditions and its recovery following injury. This understanding will contribute to the identification of strategies for maintaining the health and preventing diseases of the gastrointestinal (GI) tract. The intestinal epithelium forms the first barrier between the gut lumen and the body. It has a complex architecture, with invaginations into the intestinal wall called crypts located between finger-like projections into the lumen called villi. Several crypts surround a villus forming a crypt-villus unit; each crypt is involved in more than one unit, providing cells to more than one villus. Intestinal stem cells located at the base of each crypt proliferate and give rise to epithelial cells, which migrate to the tip of the neighbouring villi, from where they are shed into the gut lumen. In the healthy intestine, the dimensions and cell number on this crypt-villus unit remain remarkably constant during adult life. This implies a tight coordination of the numbers of crypts and villi, cell production in the crypts, cell migration along the crypt-villus axis, and cell shedding from the villus. Failure of regulation of these processes may result in tumour formation, inflammatory processes or loss of the integrity of the intestinal barrier. The subject of this proposal is gaining insight into the mechanisms underlying the maintenance of the equilibrium between crypts and villi in the intestinal epithelium and how this balance is regained after injury. However, such questions cannot currently be resolved by experimentation alone. To this end, mathematical and/or computational modelling represents an alternative framework within which to conduct in-silico experiments that complement experimental approaches. We plan to integrate computational models with experimental data to elucidate the biophysical mechanisms that coordinate cell dynamics in the epithelium.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Diet and Health, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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