Pioneering ubiquitin researcher inducted as Academy Fellow

25 May 2023
Key Researchers
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David Komander wearing a light blue shirt

Professor David Komander has been elected a Fellow of the Australian Academy of Science for his significant research contributions towards unravelling the ubiquitin system.

Ubiquitin is a small protein that acts like a “tag” to tell our cells which proteins to break down or recycle a vital process that ensures cells stay healthy and function correctly.

Prof Komander’s findings have transformed the field’s understanding of how this protein works, unlocking new research areas and leading to drug discovery projects for conditions such as Parkinson’s disease.

At a glance
Professor David Komander has been elected a Fellow of the Australian Academy of Science for his findings that have shaped our understanding of the ubiquitin system.
His key discoveries have shaped our understanding of the ubiquitin system and have been translated into drug discovery projects for conditions like Parkinson’s disease.
Prof Komander is one of 20 scientists elected into the Academy this year, recognised as one of the nation’s most distinguishes scientists for his impactful research.

After training as a structural biologist and biochemist in Germany and the UK, Prof Komander moved to WEHI in 2018 to start the first ubiquitin-focused research division in Australia.

He is credited for uncovering how broad and important the ubiquitin system is, highlighting the power and importance of ubiquitin signalling and for helping to unravel fundamental discoveries in a variety of research fields.

Prof Komander, Head of WEHI’s Ubiquitin Signalling Division, said he is both humbled and thrilled to be elected a Fellow of the Academy.

“The ubiquitin field is an extremely exciting one to work in and it has been rewarding to see what my lab has been able to uncover in the past decade,” he said.

“WEHI now has the most comprehensive ubiquitin labs in the southern hemisphere. It is amazing to see more than 50 ubiquitin researchers in one place, using state-of-the-art techniques and fostering vital collaborations to further understand the ubiquitin code.

“In recent years, my lab has leveraged our key insights to understand how ubiquitin signalling is linked to neurodegenerative disorders and other conditions like cancer, with our findings opening new avenues for drug discovery now pursued by academic and biotech efforts.

“Ubiquitin research is inherently disease agnostic, as ubiquitin regulates so many distinct disease processes. Our ultimate goal is to uncover new diagnostics and treatments to stop or delay incurable conditions, like Parkinson’s Disease and other ubiquitin-based disorders.”

The ‘Kiss of Death’ protein

Prof Komander’s research focuses on a form of protein modification called ‘ubiquitination’ which is relevant to a wide range of diseases including cancer, inflammatory diseases, Parkinson’s disease and COVID-19.

When proteins are ubiquitinated (modified with a ubiquitin ‘tag’), they are usually quickly destroyed by large cellular machines that disassemble the proteins.

This ‘kiss of death’ is an essential part of life and health, as it ensures broken proteins are removed from circulation, and signals in the body are transmitted.

While this process is essential to removing unwanted or damaged proteins, it can trigger inflammation and stress when it goes awry. Such cellular stress can lead to disease.

For almost two decades, Prof Komander’s research has focussed on unravelling different ubiquitin signals and pathways.

He has led biochemical and molecular studies that enabled research on five previously unstudied ubiquitin chain types, highlighting how complex the ubiquitin system is and its significance in regulating the way our body functions. His methods have been patented and licensed, providing many commercially available reagents.

Prof Komander’s discoveries have often focused on deubiquitinases (DUBs), which remove ubiquitin from proteins and protect proteins from being destroyed.

His work has established DUBs as drug targets to remove unwanted proteins, or to make more beneficial, ‘good’ proteins.

Drug discovery in Parkinson’s disease

Prof Komander’s work has significantly impacted the understanding of Early Onset Parkinson’s Disease (EOPD) and its link to proteins called PINK1 and Parkin, known to play critical roles in EOPD.

In 2021, his team produced a ‘live action’ view of PINK1 in exquisite molecular detail, which showed how the PINK1 progresses from when the protein is initially made, to being activated and functional. The work provided profound insights into Parkinson’s disease.

The work on PINK1 has also paved the way for developing therapeutic agents that ‘switch on’ PINK1 to eventually treat Parkinson’s disease – an incurable condition that affects more than 10 million people worldwide, including more than 80,000 Australians.

Also elected to the Australian Academy of Science this year is WEHI Honorary Fellow Professor Andrew Wilks.

Prof Wilks is CEO of Anaxis Pharma, an innovative joint venture between Synthesis Research and WEHI, focused on developing novel inhibitors/modulators of cell death, specifically an inflammatory form of programmed cell death known as necroptosis.

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