Lay summary
In healthy animals, cellular processes precisely determine the number and type of cells. One pathway, referred to as WNT signalling, is required for embryonic development and maintaining adult stem cells. Abnormal activation of WNT signalling frequently leads to cancer, with mutations commonly occurring in the core pathway regulators.
Two related enzymes, called ZNRF3 and RNF43, regulate WNT signalling by determining the abundance of WNT receptors on cell membranes. This is achieved by the attachment of a tag, called ubiquitin, which signals for the destruction of the receptors.
Our goal is to identify new interventions for cancer by elucidating how ZNRF3 and RNF43 function. We will use biochemical approaches to reveal how these enzymes attach ubiquitin to WNT receptors and how they are regulated. This work will reveal important new knowledge about WNT signalling and should provide new targets for drug development.