Ubiquitin trailblazer elected Fellow of prestigious Royal Society

Posted: 20 May 2024

WEHI division head and pioneer of ubiquitination Professor David Komander has been elected a Fellow of the esteemed Royal Society, the UK’s national science academy.

Prof Komander was recognised for his significant research contributions towards understanding ubiquitin, the ‘kiss of death’ protein which tells our cells which proteins to break down or recycle – a vital process that helps cells stay healthy and function correctly. Prof Komander’s work has helped unravel the ‘ubiquitin code’ that enables ubiquitin to perform many additional cellular functions.

He is one of only five from Australian institutes and 94 people worldwide to be elected to the Royal Society in 2024.

Prof Komander joined WEHI in 2018 to start the first ubiquitin-focused research division in Australia, following a career in structural biology and biochemistry in Germany and the UK.

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

Prof Komander said he was grateful and humbled to be elected a Fellow of the Royal Society.

“Having grown up scientifically in the UK, I have seen first-hand what impact the Fellowship had on some of my mentors, leading to some fresh focus on the big picture and the big questions,” he said.

WEHI director Professor Ken Smith said joining the Royal Society and its 350-year legacy of advancing science was a wonderful recognition of Prof Komander’s achievements.

“For almost two decades, David has dedicated his career to untangling different ubiquitin signals and pathways, growing our collective understanding of this critical cellular process,” said Prof Smith.

“David is an exemplary researcher who leads a globally recognised ubiquitin lab, and a highly regarded member of our team here at WEHI.

“We could not be more proud of all he has achieved – and the discoveries yet to come.”

Prof Komander’s work has uncovered new drug targets for neurodegenerative diseases, significantly expanding our understanding of Early Onset Parkinson’s Disease and its link to two key proteins: PINK1 and Parkin.

In 2021, Prof Komander’s team produced a ‘live action’ view of PINK1 which showed how the protein progresses from when it is initially made, to being activated and functional. The work provided fundamental insights into Parkinson’s disease.

His work on PINK1 and Parkin has also paved the way for developing therapeutic agents that can ‘switch on’ these proteins to eventually treat Parkinson’s disease – an incurable condition that affects an estimated 220,000 Australians.

Molecular ‘kiss of death’

Prof Komander’s research focuses on a form of protein modification called ‘ubiquitination’ which affects 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, ensuring broken proteins are removed from circulation and signals in the body are transmitted.

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

Importantly, ubiquitination comes in many forms, forming a complex signalling ‘code’. This code is used by all cells to move proteins within them, to change their interactions and to signal changes in the cellular environment.

Unravelling this ubiquitin code is the mission of Prof Komander, one which he has contributed significantly to along his research career.

For example, Prof Komander discovered and named OTULIN, an enzyme that plays important roles in regulating the immune system’s response to infection and inflammation, when at Cambridge in 2013.

The discovery led to the identification of a severe autoinflammatory disease, which has been named OTULIN-related autoinflammatory syndrome – or ORAS.

Research leaders and Royal Fellows

Prof Komander joins a growing list of exemplary WEHI scientists to be elected a Fellow of the Royal Society, including past institute directors Professor Suzanne Cory ACSir Gus Nossal ACSir Frank Macfarlane Burnet and Dr Charles Kellaway.

He joins Professor Jane Visvader and Professor Alan Cowman AC as current members of staff who are Royal Society Fellows.

Prof Komander, who was elected a Fellow of the Australian Academy of Science in 2023, said there remains much to learn in ubiquitin research, making it an exciting time to be in the lab.

“I am really grateful to the many people I worked with, at all stages of my career, that have impacted me as a scientist,” he said.

“In my labs in Cambridge and now WEHI, I have been lucky to work with incredibly smart and talented researchers, and I thank them all for their enthusiasm, intelligence and creativity.

“I am especially indebted to my advisors, especially Dario Alessi FRS and David Barford FRS, for their continued support, and to the WEHI community who have warmly welcomed me since 2018.”

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