Functional analysis of integrated Wnt signals for self-renewal of the human colonic epithelium

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.