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Robots help put brakes on inflammatory diseases

25 June 2024

Fully automated diagnostic techniques, including liquid handling robots, are poised to improve the lives of millions of people living with inflammatory diseases worldwide.

A landmark WEHI study has revealed new methods in detecting necroptosis, a key factor in many inflammatory diseases like psoriasis, arthritis and inflammatory bowel disease.

The findings mark a huge leap forward in our ability to diagnose necroptosis accurately. They also offer practical methods that can be easily reproduced in hospitals worldwide, giving hope for new ways to treat inflammatory diseases.

At a glance
Necroptosis is a form of cell death, one of the body’s natural processes for removing unwanted or dangerous cells. In some people this process can go awry and trigger disease.
Researchers have developed a set of automated techniques to pinpoint when and where necroptosis happens in patients.
The findings could lead to better diagnosis and personalised treatments for numerous inflammatory diseases.

Catching the cell death ‘culprit’

Necroptosis, a type of cell death associated with inflammation, has long been suspected as the ‘culprit’ driving many debilitating diseases associated with gut, skin, and lung conditions. However, identifying which cells undergo necroptosis in real-life situations has been difficult.

WEHI’s Dr Andre Samson, co-leader of the study, said the findings had cracked a challenging and hotly debated area of science.

“It is so exciting to finally be able to catch necroptosis in the act,” Dr Samson said.

The new methods precisely located necroptosis in patients with ulcerative colitis or Crohn’s disease, providing critical insights into how this cell death process contributes to various inflammatory diseases.

The findings further revealed that necroptosis responds not just to inflammation, but also to bacterial changes or immune issues.

“Among other results, we also found that when proteins like Caspase-8 cluster together in cells, it’s a sign of necroptosis,” Dr Samson said.

“This is a major leap forward in our journey to eventually delivering new medicines that can treat a long list of inflammatory diseases by stopping necroptosis.

“It helps us understand when and where necroptosis happens, both in healthy and disease situations.”

WEHI researchers Professor James Murphy, Dr Aysha Al-Ani, Dr Andre Samson and Shene Chiou.
WEHI researchers Professor James Murphy, Dr Aysha Al-Ani, Dr Andre Samson and Shene Chiou. Credit: WEHI

Diversity delivers

The study involved a meticulous and painstaking process of optimising over 300 different experimental conditions to arrive at a set of reliable robotic methods.

Study co-leader and WEHI Inflammation division head, Professor James Murphy, said a ‘perfect trio’ was behind the groundbreaking results – decades of tireless cell death research, cutting edge technology and a brilliant global team.

“We used multiple techniques, including state-of-the-art spatial transcriptomics to scrutinise and verify our results,” Prof Murphy said.

“The size and diversity of the team was also noteworthy and critical to uniting invaluable perspectives and expertise.”

The team included three PhD students – Shene Chiou, Aysha Al-Ani and Wayne Cawthorne – six departments from WEHI, spanning disciplines from advanced imaging to genomics, plus collaborators including gastroenterologists from the Royal Melbourne Hospital and bioinformaticians from Cornell University in New York.

Cells dying by necroptosis, an inflammatory form of cell death. Credit: WEHI.
Cells dying by necroptosis, an inflammatory form of cell death

Lifesaving atlas for the future

The research opens new windows to understanding the intricate mechanisms of cell death and its con-nection to inflammatory diseases.

The team behind the study referred to their work as an “atlas of necroptosis” because it provides a pre-cise map of which cells in the body are capable of undergoing necroptosis.

“We can now confidently visualise where and when necroptotic cell death can happen in the body,” said Prof Murphy.

In the spirit of collaboration, Prof Murphy emphasised that a key goal of the study was to discover a solu-tion that could be easily replicated in both the laboratory and clinical settings.

“Most importantly, researchers and clinicians around the world will now be able to use these new meth-ods, especially as liquid handling robots for immunostaining are common in hospitals and pathology departments worldwide,” he said.

“The next phase is to use these robotic methods to advance our understanding of which diseases could benefit from medicines that block necroptosis.”

The successful development of these automated methods to detect necroptosis in patients is just the be-ginning. The research team plans to extend their techniques to investigate other gut diseases, such as coeliac disease, and a broader range of inflammatory conditions of the skin, lung and kidney.

The research was supported by the National Health and Medical Research Council, the Kenneth Rainin Foundation, Anaxis Pharma and in collaboration with the Royal Melbourne Hospital and Cornell University.

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Key Researchers
Black and white photo of Aysha Al-Ani
Dr Aysha Al-Ani
Gastroenterologist
Wayne Cawthorne
PhD Student
Shene Chiou
PhD Student
Division Head
Senior Research Scientist (Laboratory)
Media Enquiries
References
An immunohistochemical atlas of necroptotic pathway expression
Journal
EMBO Molecular Medicine
DOI
10.1038/s44321-024-00074-6
Full details
WEHI Authors
Black and white photo of Aysha Al-Ani
Dr Aysha Al-Ani
Gastroenterologist
Wayne Cawthorne
PhD Student
Shene Chiou
PhD Student
Division Head
Senior Research Scientist (Laboratory)
Yi Pan
Yi Pan
Research Assistant
Black and white photo of Lachlan Whitehead
Senior Research Officer
Amanda Light
Research Assistant
Samuel Young
Samuel Young
Research Officer
Callum Sargeant
Callum Sargeant
Senior Research Officer
Leah Zhu
Senior Histologist
Dr Anne Hempel
Senior Research Officer
Research Assistant
James Rickard
James Rickard
Catherine Hall
Catherine Hall
Pradnya Gangatirkar
Pradnya Gangatirkar
Senior Research Officer
Annette Jacobsen
Annette Jacobsen
Christopher Horne
Christopher Horne
Katherine Martin
Katherine Martin
Lisa Ioannidis
Lisa Ioannidis
Diana Hansen
Diana Hansen
Senior Research Officer
Photo of Ian Wicks
Centre Head
Dr Charity Law
Senior Research Officer
Laboratory Head
Genomics Laboratory Head
Senior Research Scientist
Theme Leader
Ellen Tsui
Head, Advanced Histotechnology Facility
Division Head
Laboratory Head
Britt Christensen
Britt Christensen
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