New proteomics technique gives insights into ubiquitin signalling

August 14, 2019

Australian researchers are among the first in the world to have access to a new approach to understand intricate changes that control how proteins function in our cells in health and disease.

The new proteomics technique called 'ubiquitin clipping' allows researchers to create high-definition maps of how proteins are modified by a process called ubiquitination. The technique provides a new level of detail for understanding the role of ubiquitination in cells, and could uncover subtle changes that contribute to a range of diseases including cancer, inflammatory conditions and neurodegenerative disorders.

The research, which was published today in Nature, was led by Walter and Eliza Hall Institute researcher Professor David Komander, who undertook the work at the MRC Laboratory of Molecular Biology in Cambridge, UK.

At a glanceUbiquitin architecture

Ubiquitin is a small protein that can link to other proteins in a cell, either as a single unit or in longer straight or branched chains. Professor David Komander, who heads the Institute's recently established Ubiquitin Signalling division, said protein ubiquitination could impact all cellular processes.

"Ubiquitination can change how proteins function, potentially altering their activity, redirecting them to different parts of the cell, or regulating their interactions with other proteins. One of the best-known examples of ubiquitination is when it targets specific proteins for destruction, regulating the levels of the protein in the cell, but we now know there are many more subtle and complex roles for ubiquitin signalling," he said.

"The 'architecture' of ubiquitin chains can be complex with many branches that influence its impact on proteins, yet until now it has been almost impossible for researchers to detect and distinguish between different branching structures. This has limited the experiments that were possible to understand the role of ubiquitination in disease processes."

The new 'ubiquitin clipping' technique, which was developed by Professor Komander and his colleagues at the University of Cambridge and the University of Vienna, enables scientists to measure different ubiquitin chain architectures by pretreating protein samples, and then analysing them using electrophoresis and mass spectrometry.

"Ubiquitin clipping has enabled us to reveal a whole new level of complexity in ubiquitin signalling. In our pilot experiments, we discovered branched ubiquitin chains are much more common than previously thought. We could also study combinations of modifications on ubiquitin and other proteins - a feat that was until now rather difficult," Professor Komander said.

"This is a revolutionary technique that simplifies ubiquitin research, enabling a new level of detailed experimentation. It's the difference between describing a house based solely on the number of walls, windows and doors it has, versus looking at the detailed architectural plans."

New insights into diseases

Altered ubiquitination of proteins has been implicated in a range of diseases, including cancer, inflammatory diseases and neurodegenerative disorders such as Parkinson's disease. Professor Komander said the ubiquitin clipping technique was already being applied to study patient samples.

"My Walter and Eliza Hall Institute colleague Dr Rebecca Feltham is using ubiquitin clipping to look for protein ubiquitination patterns in samples from patients with rheumatoid arthritis, a complex inflammatory disease. This could give new insights into how this disease develops and responds to existing therapies," he said.

"Ubiquitination is also a promising target for the development of new drugs. Ubiquitin clipping will be a critical aspect of my team's drug discovery research.

"It's exciting that Australian researchers are among the first in the world to have access to ubiquitin clipping, and I'm looking forward to seeing the technique underpin many exciting discoveries, including through our collaborations with other research groups."
The research at the University of Cambridge was supported by the UK Medical Research Council, the European Research Council, the Lister Institute for Preventative Medicine (UK), the Austrian Science Foundation and a Gates Cambridge Scholarship. Professor Komander's research at the Walter and Eliza Hall Institute is currently supported by the Victorian Government.

Walter and Eliza Hall Institute

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to