Award details

FUNCTIONAL ANALYSIS OF INTEGRATED WNT SIGNALS FOR SELF-RENEWAL OF THE HUMAN COLONIC EPITHELIUM

Reference	BB/D018196/1
Principal Investigator / Supervisor	Dr Mark Williams
Co-Investigators / Co-Supervisors	Professor Andrea Munsterberg
Institution	University of East Anglia
Department	Biological Sciences
Funding type	Research
Value (£)	379,164
Status	Completed
Type	Research Grant
Start date	01/12/2006
End date	31/12/2009
Duration	37 months

Abstract

Wnt signalling pathways are emerging as master controllers of tissue renewal of skin, bone marrow and intestine. Wnt stimulation is regulated by the complex expression of secreted ligands, secreted antagonists, membrane receptor expression and downstream intracellular signalling components. Recent analysis of Wnt component expression suggests that integrated canonical and non-canonical Wnt signals regulate the self-renewal of the intestinal epithelium. Bioimaging and functional genomic approaches will be applied to a novel three dimensional model of the human colonic epithelium to study the mechanisms and role of Wnt signals in tissue renewal.

Summary

The lining of the colon is formed by millions of invaginations called crypts. The majority of cells lining the colon are renewed every 5 days or so. Stem cells continuously produce immature cell offspring at the base of each crypt, which migrate upwards. After a few days the cells reach the crypt surface and undergo cell death. To sustain the normal function of the colon lining, the rate of cell death needs to be balanced by the rate of cell production. The mechanisms that coordinate cell production and cell death in the crypt are unknown. Wnt signals have recently been demonstrated to be a dominant force in the maintenance of the epithelium. However, the identity of the Wnt factors, specific signals and cellular processes are unknown. This study will utilise a novel combination of an intact model of the colon epithelium, state-of-the-art bioimaging techniques and molecular biology that are necessary to study the cellular signals activated by each Wnt factor and determine the consequences to the constant renewal of the colonic epithelium.

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	Stem Cells
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

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search