2023 GSK Award recognises leading ubiquitin researcher

Structural biologist Professor David Komander (pictured) has been awarded the 2023 GSK Award for Research Excellence — one of the most prestigious and longstanding independently judged awards available to the Australian medical research community — in recognition of his work in elevating global understanding of the ubiquitin system, having uncovered the key principles in ubiquitin chain assembly and disassembly.

Ubiquitin is a protein that acts like a ‘tag’ to tell our cells which proteins to break down or recycle, an important ‘kiss of death’ process that helps our cells stay healthy and functional. Komander’s discoveries have allowed researchers to visualise different types of ubiquitin chains involved in recognition and disassembly of damaged proteins. This has led to new drug discovery projects across a range of conditions, including cancer, rare inflammatory diseases and Parkinson’s disease.

In particular, the study of linear ubiquitin chains and their role in inflammation processes has led Komander to the discovery of a new protein that helps control inflammation, which was named OTULIN. This discovery further resulted in identification of a severe autoinflammatory disease, named OTULIN-related autoinflammatory syndrome (ORAS) — a very rare genetic disease which can be life-threatening if not treated.

As Head of the Ubiquitin Signalling Division at WEHI, Komander and his team have recently been researching the link between early-onset Parkinson’s disease and two proteins called PINK1 and Parkin, as part of their studies into the ubiquitin system. Komander’s research in this field has sparked collaborative work in the WEHI Parkinson’s Disease Research Centre.

“Early-onset Parkinson’s can be caused by genetic mutations that alter the function of key proteins,” Komander said. “By understanding the molecular structures of these mutated proteins and monitoring how these proteins become activated and function, we have gained powerful insights into how Parkinson’s disease develops. Along the way, we contributed to some of the most important breakthroughs in the field in the last decade.”

“Defects in ubiquitin signalling are at the heart of neurodegenerative diseases such as Parkinson’s,” added Associate Professor Grant Dewson, Head of the Parkinson’s Disease Research Centre. “David’s research has provided key insights into this and the role of PINK1 and Parkin in this highly complex disease. These proteins are the focus of international drug discovery efforts to stop or slow the progression of Parkinson’s, and David’s research has unlocked this potential.”

Komander said the $100,000 grant that comes with the GSK Award for Research Excellence will help take the team’s research to the next level, especially as there are many areas of ubiquitination that have been under-researched.

“Expanding our research into other molecules will open an entire new realm of what ubiquitination might be able to do,” he said. “This grant will provide us with critical support as we take our research to the next level and build new methods for measuring ubiquitin modifications.”

The award was presented last week at Research Australia’s Health and Medical Research Awards in Sydney. Dr Alan Paul, Medical Director at GSK Australia, said GSK is proud to support local researchers who are at the forefront of improving health outcomes for patients in Australia and around the world.

“Professor Komander’s work is an outstanding example of how home-grown innovation is transforming our understanding and potential treatment of diseases like Parkinson’s that we once believed were incurable,” Paul said. “We are excited to support David and his team as they continue their critical research into the ubiquitin system.”