- A slice through the crystal structure of Notum (grey) revealing the large cavity that Notum uses to dock onto the Wnt ‘finger’ (orange).
- Division of Structural Biology (STRUBI), Oxford University
Professor Yvonne Jones is Joint Head of the Division of Structural Biology (STRUBI) in the Nuffield Department of Clinical Medicine at Oxford University; she headed a team whose work was central to the discovery of Notum’s role. She comments: “It has been tremendously exciting to discover that Notum has this completely unsuspected role, and, using Diamond, to capture atomic level details of it at work.”
In a multi-disciplinary collaboration scientists uncovered the significance of Notum through a range of experimental methods. They explored the protein’s behaviour in fruit fly genetics at the MRC NIMR, and studied the structure and function at STRUBI in Oxford. The team from STRUBI collected X-ray data to determine the three dimensional structure of Notum using the macromolecular crystallography (MX) beamlines i02, i03, i04, i04-1 and i24 at Diamond. The research was funded by a range of partners including Cancer Research UK and the Wellcome Trust*.
The vital work of these scientists in uncovering the unknown properties of this once overlooked protein is likely to have a real impact on research in the years to come. The newly-discovered properties of Notum and its role in the control of Wnt give it a heretofore unrealised significance in cancer and neurological research, opening the door to new studies and new opportunities for discovery.
* Funders in full: CRUK, MRC, WT, ERC, UK Research Council Basic Technology Initiative, Marie Curie IEF, Japan Society for the Promotion of Science, University of Oxford Clarendon Fund and Somerville College Scholarships.