First up, can you tell us a little bit about your work?
Our lab works on the Wnt signalling pathway, one of the key morphogen signalling pathways in multicellular organisms, which play a central role from embryonic development (cell fate determination, cell polarity, axis determination) all the way through adulthood (tissue homeostasis, regeneration). We are particularly interested in understanding the molecular mechanisms that lead to pathway activation at the plasma membrane upon binding of the secreted morphogen, Wnt, to the Frizzled and LRP receptors. Towards this aim we use a variety of methodologies at the core being protein biochemistry, structural biology, and some cell biology.
It sounds like the paper you published prior to your Wellcome award really stirred up some feelings in the Wnt signalling world. How did you know you were on the right track with your work?
This was one of those high risk, high reward projects which at first glance seemed for many in the Wnt field as overly ambitious. This stemmed primarily from the past knowledge that several Wnt signalling labs have tried to do what we were aiming to do but didn’t succeed. We ‘just’ took a pragmatic approach and thought that there have been enough advancements in the technology and reagents which would make the project feasible. Over the first 2 years, the project was moving forward but we still were not completely sure about the overall feasibility of the project. In the end it boiled down to a set of key technical insights which swung open the doors and enabled us to in vitro reconstituted and dissect part of the Wnt signalling pathway.
Read the full interview on the Department of Physiology, Anatomy and Genetics website.