-

About the lab

Cells in the human body must quickly respond to countless challenges like changes in the environment, damage to cellular components or infections by changing their internal signalling pathways. Cells do this by modifying or degrading existing proteins by attaching small markers (post-translational modifications). The small protein ubiquitin is one such marker and is attached by enzymes called E3 ubiquitin ligases.

The human genome encodes for more than 700 E3 ubiquitin ligases that each act on very specific targets and regulate fundamental cellular processes. Their importance for cellular health is underscored by the fact that mutations in E3 ligases can cause a vast range of human diseases such as inflammation, cancer, and autoimmune or neurodegenerative diseases. E3 ligases are thus new targets for innovative treatment options in these conditions.

We study E3 ubiquitin ligases to understand their functions in the human body, their roles in human diseases and to lay the groundwork for drug discovery to target these diseases.

Impact

Our most recent impact is in understanding the catalytic mechanism of the RBR E3 ubiquitin ligase family and its allosteric regulation by ubiquitin chains. In the past few years, we have contributed many key insights into these processes (Lechtenberg et al., Nature 2016; Cotton et al. Molecular Cell 2022; Wang & Cotton et al, Nature Communications 2023).

We are now able to leverage these molecular insights to investigate the biological functions of this enzyme family, including how mutations in the RBR E3 ligase RNF216 leads to the neurodegenerative disease Gordon Holmes Syndrome.

Lab research projects

Lab team

The Lechtenberg lab is a multidisciplinary team that combines structural biology with biochemistry, cell biology, and mass spectrometry.

We closely collaborate with other laboratories in the Ubiquitin Signalling division and WEHI. We are always interested to hear form enthusiastic candidates at all career stages who share our love for all things ubiquitin and E3 ubiquitin ligases.

6 members
Jenny Jiou
Research Officer
Jackson Zhao
Honours Student
PhD Student
Erin McGowan
Research Officer
Interested in supporting our research?

Your support will help WEHI’s researchers make discoveries and find treatments to ensure healthier, longer lives for you and your loved ones.

Contact our friendly team to find out how you can help.