Quantitative Biology of Wnt-R-spondin signalling in colon cancer

Colon cancer is associated with increased sensitivity to Wnt signalling. Eighty five per cent of colon cancer cells have a mutation which leads to the truncation of the tumour suppressor protein APC, a critical relay for Wnt signalling. R-spondin is a potent stimulator of the intestinal mucosa and appears to associate with the Wnt receptor complex to enhance signalling.

This project will study how R-spondin potentiates Wnt signalling. Specifically, the effects of R-spondin on the dynamics of Wnt receptor complex, and in particular β-catenin levels and location in normal and APC-defective cells, will be investigated using cell culture, western-blotting and immunofluorescent microscopy.

These measurements will improve our understanding of R-spondin’s roles in Wnt signalling and provide information for developing computational Wnt/R-spondin models.

This project will be supervised by:
Dr Chin Wee Tan ([Email Address Removed])
Professor Antony Burgess ([Email Address Removed]) http://www.wehi.edu.au/faculty_members/professor_antony_burgess


Research interests

Understanding the complex mechanisms involved in colon cancer progression is critical to the successful identification of therapeutics. A computational systems biology approach to assess the non-intuitive complex behaviours of cellular signalling pathways will provide an integrated perspective of cancer progression. Our laboratory is introducing such an approach (using colon crypt culture, quantitative imaging and modelling techniques) to build computational models for human colon cells and in the process, bridge the gap between experiments, models and clinical therapeutics.

An integrated signalling (e.g. Wnt) model of colon cells and the discovery of new molecular targets using this approach will be an important step toward gaining insights into colon cancer biology. We anticipate these studies and models will improve opportunities to identify potential drug targets and aid in focussing therapeutic developments for the prevention and treatment of colon cancer.