Structural basis of β-catenin-independent Wnt signalling

Structural basis of β-catenin-independent Wnt signalling

Project details

Wnt ligands are a family of secreted glycoproteins that regulate many processes of cell proliferation, polarity, differentiation, and migration. Wnt signalling is absolutely crucial for embryonic development and in adults its dysregulation underlies the progression of many cancers. Wnt signalling is mediated by Wnt proteins that activate Frizzled receptors (FZD). Different combinations of Wnts/FZD/co-receptors can elicit different signalling outcomes through the engagement of different cellular partners.

This project will specifically focus on understanding the structural basis of how Wnt binding to FZD leads to G protein coupling. We will use a wide range of molecular biology and biochemical techniques to create a stable complex suitable for structure determination using cryo-electron microscopy. Once successful, the student will learn sample preparation, imaging, data processing, and structure analysis.

About our research group

Our lab is interested in understanding the structural mechanisms of Wnt signalling. Wnt signalling pathways control many aspects of cell development, differentiation, organogenesis, and cell polarity and their disruption in embryos leads to developmental defects and in adults to pathologies in cell division, differentiation, and repair. Because of this, the Wnt signalling pathway is an important drug target for a variety of cancers with many drugs in phase I and II clinical trials. 

We are interested in understanding the molecular-level details of different aspects of Wnt signalling, from Wnt maturation to signalling complexes at the membrane and formation of large multi-protein assemblies within the cells. We are employing molecular biology, biochemistry, biophysics, pharmacology, x-ray crystallography, and cryo-electron microscopy.

 

Email supervisors

 

Researchers:

Dr Alisa Glukhova

Dr Alisa Glukhova in a laboratory
Dr
Alisa
Glukhova
Laboratory Head

Project Type: