A leading structural biologist and Head of the Ubiquitin Signalling Division at WEHI, Prof Komander 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.

Prof 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 the researcher 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, which has been named the OTULIN-related autoinflammatory syndrome (ORAS). ORAS is a very rare genetic disease, which can be life-threatening if not treated.

Prof Komander and his team have recently been researching the link between early onset Parkinson’s disease, a chronic and progressive disorder of the nervous system, and two proteins called PINK1 and Parkin as part of their studies into the ubiquitin system.

“Early onset Parkinson’s can be caused by genetic mutations that alter the function of key proteins,” Prof 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.”

Prof Komander’s research in this field has sparked collaborative work in the WEHI Parkinson’s Disease Research Centre.

The centre works with movement disorder clinicians and consults with the Parkinson’s community to better understand the needs of those living with Parkinson’s and to guide research.

Associate Professor Grant Dewson, Head of the Parkinson’s Disease Research Centre said:

“Parkinson’s is the second most prevalent neurodegenerative condition, but its incidence is increasing faster than other neurological disorders. Importantly, there are no drugs that can stop disease progression.”

“Defects in ubiquitin signalling are at the heart of neurodegenerative diseases such as Parkinson’s. 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.”

There are estimated to be more than 200,000 people currently living with Parkinson’s disease in Australia, with one in five being diagnosed before the age of 50.

Prof Komander says his team’s work on the ubiquitin code is paving the way for the development of new therapeutic agents to treat Parkinson’s disease, which currently has no cure.

“We are really getting out of the academic mindset and moving towards more translatable outcomes. Enhancing our knowledge in this area has the potential to drive transformative improvements in health outcomes for patients living with other incurable diseases, including cancer,” said Prof Komander.

Prof Komander said the $100,000 AUD grant that comes with the GSK Award for Research Excellence will help take their 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. 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.

“It’s an exciting time to be working within the field of ubiquitination. I am honoured to be named the 2023 recipient of the GSK Award for Research Excellence and have our work recognised in this way.”

The 2023 GSK Award for Research Excellence was presented to Prof Komander at Research Australia’s Health and Medical Research Awards in Sydney this week.

Dr Alan Paul, Medical Director at GSK Australia, said GSK is proud to support local Australian researchers who are at the forefront of improving health outcomes for patients in Australia and around the world.

“Prof 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,” said Dr Paul.

“We are excited to support David and his team as they continue their critical research into the ubiquitin system.”

The GSK Award for Research Excellence is one of the most prestigious and longstanding independently judged awards available to the Australian medical research community. It has been awarded since 1980, with over $3 million awarded to local researchers since its inception.