Cells are wet 'computers' for processing environmental information and forming appropriate
responses. Instead of wire, diodes and capacitors, cells use networks of chemical reactions
to transmit and modify environmental signals to the cell nucleus or to neighbouring cells.
These signal-transduction pathways should make decisions as to the correct response of the cell.
The Wnt signaling pathway plays a critical role in development, particularly in directing cell
attachments and proliferation. In the adult, it is this same signaling pathway that is believed
to be reactivated in many cancers, including colon cancer. In other words, the Wnt signaling
pathway is crucial for healthy development, but in adult cells deregulated Wnt signaling can
lead to tumourigenesis. The hallmarks of malignant cancer are inappropriate proliferation,
invasion and metastasis. In order for this to proceed, cancer cells must be capable of
switching (deciding) between a quiescent to a proliferation mode and also switching between
cell proliferation and an invasive mode (with cells detaching from the primary tumour). Secondary
tumours grow when the invading cells return back to a proliferation mode. The Wnt signaling
pathway is involved in each of these stages of malignant cancer development quiescence, cell
proliferation and cell-cell adhesion. Despite being fundamental to cancer cell behaviour, the
switching between these various states of the Wnt signaling pathway is still poorly understood,
and as such represents a key limitation to future progress in understanding a wide range of cancers.
Therefore, the primary aim of this project is to understand the switching between various states
of the Wnt signaling pathway. The approach employed is a combination of mathematically modeling
(i.e. using computational system-biology methods), coupled with experimental molecular
biology (performed by research partners at the Ludwig Institute for Cancer Research in Melbourne).
- 2009-2011, NHMRC, Simulations of colon cancer, Tony Burgess, David Smith and Bruce Gardiner, $528,750