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Structural Biology of Wnt Signalling

About the lab

Our laboratory aims to understand the molecular details of cell signalling pathways involved in cell development, fate determination, and polarity. These processes are important in embryonic development and maintenance of healthy tissues in adults. Because of this, their dysregulation underlies the cause of many human cancers.

Specifically, we are interested in understanding the molecular details of different steps in Wnt pathways. Wnt signalling is initiated by Wnts that bind to their receptors and co-receptors, leading to different cellular responses. Multiple steps of the Wnt pathways have been explored as therapeutic targets for cancer treatment, however, due to the extreme complexity and importance of Wnt signalling for normal tissue homeostasis, its safe and selective targeting remains a challenge.

We are 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 ones that are already in clinical trials.

Our mission

Our mission is to facilitate drug discovery by leveraging structural biology to better understand the structure and function of signaling proteins.

Impact

Since its establishment in 2020, our laboratory has determined the highest resolution structure of the key Wnt-lipidating enzyme, Porcupine (manuscript in preparation), as well as the first structure of the lipid-modifying enzyme 12-lipoxygenase (manuscript under review) by cryo-EM.

Through collaborations with other laboratories at WEHI we have contributed to understanding how Sars-CoV-2 spike protein is neutralised by biologics (PMID 36213007, 34610292 and 33893175), the activation mechanism of PINK-1 (PMID 34933320). Our collaborations with Monash institute of Pharmaceutical Sciences contributed to understanding of ligand binding at the G protein coupled receptors and ion channels (multiple manuscripts under review and in preparation).

Highlights

The Glukhova Lab team at a restaurant

Lab research projects

Lab team

Our team collaborates with other labs at WEHI (Tham, Kommander and Kershaw labs), at Monash Institute for Pharmaceutical sciences (Thal lab), Karolinska Institutet (Schulte lab), University of California Santa Cruz (Holman lab) and University of Michigan (Holinstat lab).

8 members
Haripriya Ramakrishnan
PhD Student
Tin Nguyen
Honours Student
PhD Student
Prof Michael Lawrence
Honorary Research Fellow
Joshua Prendergast
Research Assistant
Research Officer
Dr Nicholas Kirk
Senior Research Officer
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