Project details

Wnt proteins are essential for many cell processes, including differentiation and migration. Porcupine (PORCN) is a transmembrane protein that modifies all Wnts with a fatty molecule, which is crucial for Wnt secretion and activity. Because of this, PORCN inhibitors show potential for treating various types of human cancers. Using cryo-EM, we achieved the highest resolution PORCN structure (2.5 Å) with a small molecule inhibitor. This student project will expand upon our PORCN work and employ cryo-EM to determine the PORCN-Wnt complex structure, aiming to understand Wnt modification by PORCN at the molecular level.

About our research group

The Glukhova laboratory aims to understand the molecular details of cell signalling pathways involved in cell development, fate determination, and polarity. Specifically, we are interested in understanding the molecular details of the Wnt pathway due to its relevance in cancer. However, due to the extreme complexity and importance of Wnt signalling for normal tissue homeostasis, its safe and selective targeting remains a challenge.

The Glukhova laboratory is combining cryo-electron microscopy and x-ray crystallography with biochemical, biophysical and pharmacological assays to gain insights into the atomic-level details of individual proteins as well as large complexes involved in Wnt signal transduction. Such detailed understanding is crucial for the development of novel therapeutics and improving those already in clinical trials.