- About
- Strategic Plan
- Structure
- Governance
- Scientific divisions
- ACRF Cancer Biology and Stem Cells
- ACRF Chemical Biology
- Advanced Technology and Biology
- Bioinformatics
- Blood Cells and Blood Cancer
- Clinical Translation
- Epigenetics and Development
- Immunology
- Infectious Diseases and Immune Defence
- Inflammation
- Personalised Oncology
- Population Health and Immunity
- Structural Biology
- Ubiquitin Signalling
- Laboratory operations
- Funding
- Annual reports
- Human research ethics
- Scientific integrity
- Institute life
- Career opportunities
- Business Development
- Collaborators
- Suppliers
- Publications repository
- Awards
- Discoveries
- Centenary 2015
- History
- Contact us
- Research
- Diseases
- Cancer
- Development and ageing
- Immune health and infection
- Research fields
- Research technologies
- Research centres
- People
- Alistair Brown
- Anne-Laure Puaux
- Assoc Prof Joanna Groom
- Associate Profesor Ian Majewski
- Associate Professor Aaron Jex
- Associate Professor Alyssa Barry
- Associate Professor Andrew Webb
- Associate Professor Chris Tonkin
- Associate Professor Daniel Gray
- Associate Professor Diana Hansen
- Associate Professor Edwin Hawkins
- Associate Professor Ethan Goddard-Borger
- Associate Professor Gemma Kelly
- Associate Professor Grant Dewson
- Associate Professor Isabelle Lucet
- Associate Professor James Vince
- Associate Professor Jason Tye-Din
- Associate Professor Jeanne Tie
- Associate Professor Jeff Babon
- Associate Professor Joan Heath
- Associate Professor John Wentworth
- Associate Professor Justin Boddey
- Associate Professor Kate Sutherland
- Associate Professor Marie-Liesse Asselin-Labat
- Associate Professor Matthew Ritchie
- Associate Professor Melissa Call
- Associate Professor Melissa Davis
- Associate Professor Misty Jenkins
- Associate Professor Nawaf Yassi
- Associate Professor Oliver Sieber
- Associate Professor Peter Czabotar
- Associate Professor Rachel Wong
- Associate Professor Rhys Allan
- Associate Professor Rosie Watson
- Associate Professor Ruth Kluck
- Associate Professor Sandra Nicholson
- Associate Professor Seth Masters
- Associate Professor Sumitra Ananda
- Associate Professor Tim Thomas
- Associate Professor Tracy Putoczki
- Chela Niall
- Deborah Carr
- Dr Alisa Glukhova
- Dr Anna Coussens
- Dr Ashley Ng
- Dr Belinda Phipson
- Dr Ben Tran
- Dr Bernhard Lechtenberg
- Dr Brad Sleebs
- Dr Drew Berry
- Dr Gwo Yaw Ho
- Dr Hamish King
- Dr Hui-Li Wong
- Dr Jacqui Gulbis
- Dr Kelly Rogers
- Dr Lucy Gately
- Dr Margaret Lee
- Dr Mary Ann Anderson
- Dr Maryam Rashidi
- Dr Matthew Call
- Dr Nadia Davidson
- Dr Philippe Bouillet
- Dr Rebecca Feltham
- Dr Rory Bowden
- Dr Samir Taoudi
- Dr Shabih Shakeel
- Dr Shalin Naik
- Dr Sheau Wen Lok
- Dr Stephin Vervoort
- Dr Yunshun Chen
- Guillaume Lessene
- Helene Martin
- Joh Kirby
- Kaye Wycherley
- Keely Bumsted O'Brien
- Mr Mark Eaton
- Mr Simon Monard
- Mr Steve Droste
- Ms Carolyn MacDonald
- Professor Alan Cowman
- Professor Andreas Strasser
- Professor Andrew Lew
- Professor Andrew Roberts
- Professor Anne Voss
- Professor Clare Scott
- Professor David Huang
- Professor David Komander
- Professor David Vaux
- Professor Doug Hilton
- Professor Geoff Lindeman
- Professor Gordon Smyth
- Professor Ian Wicks
- Professor Ivo Mueller
- Professor James McCarthy
- Professor James Murphy
- Professor Jane Visvader
- Professor Jerry Adams
- Professor John Silke
- Professor Ken Shortman
- Professor Leanne Robinson
- Professor Leonard C Harrison
- Professor Lynn Corcoran
- Professor Marc Pellegrini
- Professor Marco Herold
- Professor Marnie Blewitt
- Professor Melanie Bahlo
- Professor Mike Lawrence
- Professor Nicos Nicola
- Professor Peter Colman
- Professor Peter Gibbs
- Professor Phil Hodgkin
- Professor Sant-Rayn Pasricha
- Professor Stephen Nutt
- Professor Suzanne Cory
- Professor Terry Speed
- Professor Tony Papenfuss
- Professor Wai-Hong Tham
- Professor Warren Alexander
- Diseases
- Education
- PhD
- Honours
- Masters
- Clinician-scientist training
- Undergraduate
- Student research projects
- A new regulator of 'stemness' to create dendritic cell factories for immunotherapy
- Advanced imaging interrogation of pathogen induced NETosis
- Cancer driver deserts
- Cryo-electron microscopy of Wnt signalling complexes
- Deciphering the heterogeneity of breast cancer at the epigenetic and genetic levels
- Developing drugs to block malaria transmission
- Developing new computational tools for CRISPR genomics to advance cancer research
- Developing novel antibody-based methods for regulating apoptotic cell death
- Discovering novel paradigms to cure viral and bacterial infections
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Do membrane forces govern assembly of the deadly apoptotic pore?
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- E3 ubiquitin ligases in neurodegeneration, autoinflammation and cancer
- Engineering improved CAR-T cell therapies
- Epigenetic biomarkers of tuberculosis infection
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- Genomic rearrangement detection with third generation sequencing technology
- How does DNA damage shape disease susceptibility over a lifetime?
- How does DNA hypermutation shape the development of solid tumours?
- How platelets prevent neonatal stroke
- Human lung protective immunity to tuberculosis
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of dysregulated Tom40 in neurodegeneration
- Investigating the role of mutant p53 in cancer
- Lupus: proteasome inhibitors and inflammation
- Machine learning methods for somatic genome rearrangement detection
- Malaria: going bananas for sex
- Measurements of malaria parasite and erythrocyte membrane interactions using cutting-edge microscopy
- Measuring susceptibility of cancer cells to BH3-mimetics
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Mutational signatures of structural variation
- Naturally acquired immune response to malaria parasites
- Predicting the effect of non-coding structural variants in cancer
- Revealing the epigenetic origins of immune disease
- Reversing antimalarial resistance in human malaria parasites
- Structural and functional analysis of DNA repair complexes
- Targeting human infective coronaviruses using alpaca antibodies
- Towards targeting altered glial biology in high-grade brain cancers
- Uncovering the real impact of persistent malaria infections
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding how malaria parasites sabotage acquisition of immunity
- Understanding malaria infection dynamics
- Understanding the mechanism of type I cytokine receptor activation
- Unveiling the heterogeneity of small cell lung cancer
- Using alpaca antibodies to understand malaria invasion and transmission
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to cross the blood brain barrier for drug delivery
- Using structural biology to understand programmed cell death
- School resources
- Frequently asked questions
- Student profiles
- Abebe Fola
- Andrew Baldi
- Anna Gabrielyan
- Bridget Dorizzi
- Casey Ah-Cann
- Catia Pierotti
- Emma Nolan
- Huon Wong
- Jing Deng
- Joy Liu
- Kaiseal Sarson-Lawrence
- Komal Patel
- Lilly Backshell
- Megan Kent
- Naomi Jones
- Rebecca Delconte
- Roberto Bonelli
- Rune Larsen
- Runyu Mao
- Sarah Garner
- Simona Seizova
- Wayne Cawthorne
- Wil Lehmann
- Miles Horton
- Alexandra Gurzau
- Student achievements
- Student association
- Learning Hub
- News
- Donate
- Online donation
- Ways to support
- Support outcomes
- Supporter stories
- Rotarians against breast cancer
- A partnership to improve treatments for cancer patients
- 20 years of cancer research support from the Helpman family
- A generous gift from a cancer survivor
- A gift to support excellence in Australian medical research
- An enduring friendship
- Anonymous donor helps bridge the 'valley of death'
- Renewed support for HIV eradication project
- Searching for solutions to muscular dystrophy
- Supporting research into better treatments for colon cancer
- Taking a single cell focus with the DROP-seq
- WEHI.TV
Link found between cell death and inflammatory disease
12 May 2014
O'Donnell (L-R) were part of an institute team that
showed cell death by necroptosis could be the
underlying cause of inflammatory disease
A team of Melbourne researchers has shown a recently discovered type of cell death called necroptosis could be the underlying cause of inflammatory disease.
The research team discovered that a previously identified molecule involved in necroptosis, called RIPK1, was essential for survival by preventing uncontrolled inflammation. This finding could lead to future treatments for inflammatory diseases including Crohn’s disease, rheumatoid arthritis and psoriasis.
The researchers, from the Walter and Eliza Hall Institute, also discovered that the ‘survival’ molecule RIPK1 acts as the ‘gatekeeper’ between cell life and death. In a paper published in the journal Cell, they reveal RIPK1 is essential for a cell’s decision to live or die, and in choosing how to die.
Institute researchers Associate Professor John Silke from the Cell Signalling and Cell Death division, Dr Motti Gerlic from the Inflammation division and Dr Ben Croker led the project, working with PhD students Mr James Richard, Ms Joanne O’Donnell and Mr Joseph Evans. Associate Professor Silke said the team had shown for the first time that RIPK1 (receptor interacting protein kinase 1) was a master controller of cell life and death.
“We showed that, in the body, RIPK1 is not only essential for initiating necroptosis, but also for inhibiting necroptosis and the runaway inflammation that can cause severe tissue damage,” Associate Professor Silke said. “We also found that it played a role in another type of programmed cell death called apoptosis. Our research highlighted that RIPK1 is the gatekeeper that controls whether a cell lives or dies, and the decision it makes on how to die.”
Necroptosis is a type of ‘controlled’ death that instructs a cell to die while stimulating an inflammatory reaction to let the immune system know something has gone wrong. However when this cell death pathway begins to spiral out of control, it can lead to inflammatory disease. Necroptosis has also been implicated in neurodegenerative disease, brain injuries caused by blood loss, and some viral infections.
Dr Gerlic said their study provided the first evidence that RIPK1 was essential for inhibiting necroptosis. “This research puts a new dogma on the table about RIPK1 and its role in controlling or inhibiting necroptosis,” Dr Gerlic said. “It is also the first time that we have shown necroptosis and the molecules involved actually induce inflammatory disease, suggesting that targeting this pathway could be useful for treating human conditions such as psoriasis, rheumatoid arthritis and Crohn’s disease.”
Associate Professor Silke said necroptosis was a newly discovered type of cell death that had only really been studied in the past five years. “When our time comes to die, we don’t have a choice,” he said. “However cells make this choice all the time – not only whether they die, but also how they die. They can choose to die quietly, or they can make a fuss. Necroptosis is their way of letting everyone else know that they are dying and help is needed usually when something has gone wrong such as a viral infection.”
Dr Gerlic said the research team had also shown RIPK1 played other important roles in the body. “As part of the research we found that RIPK1 was essential for keeping blood stem cells alive after bone marrow transplant,” he said. “This finding is particularly important when considering treatments that target RIPK1, as it could have unwanted side-effects for other cells in the body. Therefore it is important to ensure any potential drugs are properly investigated for any off-target effects.”
Associate Professor Silke said the institute was already capitalising on its expertise in necroptotic cell death with a drug discovery program to identify small molecules that could target molecules downstream of RIPK1 in the necroptotic pathway, such as MLKL (mixed lineage kinase domain-like).
The research was supported by the Australian National Health and Medical Research Council, Thomas William Francis & Violet Coles Trust and the Victorian Government. Mr Rickard and Ms O’Donnell are enrolled as PhD students through The University of Melbourne, and Mr Evans is enrolled through La Trobe University.
Further information:
Liz Williams
Media and Publications Manager
P: + 61 3 9345 2928
M: +61 428 034 089
E: williams@wehi.edu.au