- 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 Andrew Webb
- Associate Professor Chris Tonkin
- 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 Jeff Babon
- Associate Professor Joan Heath
- Associate Professor John Wentworth
- Associate Professor Justin Boddey
- Associate Professor Kate Sutherland
- Associate Professor Kelly Rogers
- Associate Professor Marie-Liesse Asselin-Labat
- Associate Professor Melissa Call
- Associate Professor Misty Jenkins
- Associate Professor Nawaf Yassi
- Associate Professor Oliver Sieber
- Associate Professor Rachel Wong
- Associate Professor Rhys Allan
- Associate Professor Rosie Watson
- Associate Professor Ruth Kluck
- Associate Professor Shalin Naik
- 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 Jim Whittle
- Dr Lucy Gately
- Dr Margaret Lee
- Dr Mary Ann Anderson
- Dr Maryam Rashidi
- Dr Matthew Call
- Dr Nadia Davidson
- Dr Nadia Kershaw
- Dr Philippe Bouillet
- Dr Rebecca Feltham
- Dr Rory Bowden
- Dr Samir Taoudi
- Dr Sarah Best
- Dr Saskia Freytag
- Dr Shabih Shakeel
- Dr Sheau Wen Lok
- Dr Stephin Vervoort
- Dr Yunshun Chen
- Guillaume Lessene
- Helene Martin
- Joh Kirby
- Kaye Wycherley
- Keely Bumsted O'Brien
- Mr Simon Monard
- Mr Steve Droste
- Ms Carolyn MacDonald
- Professor Alan Cowman
- Professor Andreas Strasser
- Professor Andrew Roberts
- Professor Anne Voss
- Professor Clare Scott
- Professor Daniel Gray
- 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 Jeanne Tie
- Professor Jerry Adams
- Professor John Silke
- Professor Ken Shortman
- Professor Leanne Robinson
- Professor Leonard C Harrison
- Professor Lynn Corcoran
- Professor Marnie Blewitt
- Professor Matthew Ritchie
- Professor Melanie Bahlo
- Professor Melissa Davis
- Professor Mike Lawrence
- Professor Nicos Nicola
- Professor Peter Colman
- Professor Peter Czabotar
- Professor Peter Gibbs
- Professor Phil Hodgkin
- Professor Sandra Nicholson
- Professor Sant-Rayn Pasricha
- Professor Seth Masters
- 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 multi-pronged approach to targeting myeloproliferative neoplasms
- A new paradigm of machine learning-based structural variant detection
- A whole lot of junk or a treasure trove of discovery?
- Advanced imaging interrogation of pathogen induced NETosis
- Analysing the metabolic interactions in brain cancer
- Atopic dermatitis causes and treatments
- Boosting the efficacy of immunotherapy in lung cancer
- Building a cell history recorder using synthetic biology for longitudinal patient monitoring
- Characterisation of malaria parasite proteins exported into infected liver cells
- Deciphering the heterogeneity of the tissue microenvironment by multiplexed 3D imaging
- Defining the mechanisms of thymic involution and regeneration
- Delineating the molecular and cellular origins of liver cancer to identify therapeutic targets
- Developing computational methods for spatial transcriptomics data
- Developing drugs to block malaria transmission
- Developing models for prevention of hereditary ovarian cancer
- Developing statistical frameworks for analysing next generation sequencing data
- Development and mechanism of action of novel antimalarials
- Development of novel RNA sequencing protocols for gene expression analysis
- Discoveries in red blood cell production and function
- Discovering epigenetic silencing mechanisms in female stem cells
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Dissecting mechanisms of cytokine signalling
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- Epigenetic biomarkers of tuberculosis infection
- Epigenetics – genome wide multiplexed single-cell CUT&Tag assay development
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Exploiting the cell death pathway to fight Schistosomiasis
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- How do nutrition interventions and interruption of malaria infection influence development of immunity in sub-Saharan African children?
- Human lung protective immunity to tuberculosis
- Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways
- Innovating novel diagnostic tools for infectious disease control
- Integrative analysis of single cell RNAseq and ATAC-seq data
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigation of a novel cell death protein
- Malaria: going bananas for sex
- Mapping spatial variation in gene and transcript expression across tissues
- Mechanisms of Wnt secretion and transport
- Multi-modal computational investigation of single-cell communication in metastatic cancer
- Nanoparticle delivery of antibody mRNA into cells to treat liver diseases
- Naturally acquired immune response to malaria parasites
- Organoid-based discovery of new drug combinations for bowel cancer
- Organoid-based precision medicine approaches for oral cancer
- Removal of tissue contaminations from RNA-seq data
- Reversing antimalarial resistance in human malaria parasites
- Role of glycosylation in malaria parasite infection of liver cells, red blood cells and mosquitoes
- Screening for novel genetic causes of primary immunodeficiency
- Single-cell ATAC CRISPR screening – Illuminate chromatin accessibility changes in genome wide CRISPR screens
- Spatial single-cell CRISPR screening – All in one screen: Where? Who? What?
- Statistical analysis of single-cell multi-omics data
- Structural and functional analysis of epigenetic multi-protein complexes in genome regulation
- Structural basing for Wnt acylation
- Structure, dynamics and impact of extra-chromosomal DNA in cancer
- Targeted deletion of disease-causing T cells
- Targeting cell death pathways in tissue Tregs to treat inflammatory diseases
- The cellular and molecular calculation of life and death in lymphocyte regulation
- The role of hypoxia in cell death and inflammation
- The role of ribosylation in co-ordinating cell death and inflammation
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding cellular-cross talk within a tumour microenvironment
- Understanding the genetics of neutrophil maturation
- Understanding the roles of E3 ubiquitin ligases in health and disease
- Unveiling the heterogeneity of small cell lung cancer
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to understand malaria invasion and transmission
- Using structural biology to understand programmed cell death
- Validation and application of serological markers of previous exposure to malaria
- School resources
- Frequently asked questions
- Student profiles
- Abebe Fola
- Andrew Baldi
- Anna Gabrielyan
- Ashley Weir
- Bridget Dorizzi
- Casey Ah-Cann
- Catia Pierotti
- Emma Nolan
- Huon Wong
- Jasmine Rou
- Jing Deng
- Joy Liu
- Kaiseal Sarson-Lawrence
- Komal Patel
- Krishneel Prasa
- Lilly Backshell
- Malvika Kharbanda
- Megan Kent
- Naomi Jones
- Pailene Lim
- Rebecca Delconte
- Roberto Bonelli
- Rune Larsen
- Runyu Mao
- Sarah Garner
- Simona Seizova
- Sophie Collard
- Wayne Cawthorne
- Wil Lehmann
- Yanxiang Meng
- Zhong Yan Gan
- 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 generous vision for impactful medical research
- A gift to support excellence in Australian medical research
- An enduring friendship
- Anonymous donor helps bridge the 'valley of death'
- Philanthropy through the power of sisterhood
- 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
- Donors
- WEHI.TV
Fine-tuning cell death: new component of death machinery revealed
26 November 2018
An important component of the microscopic machinery that drives cell death has been identified by Walter and Eliza Hall Institute scientists.
Grant Dewson and Professor David Huang have revealed an
important new detail about how cells die.
Studying the ‘pro-death’ machinery that forces damaged, diseased or unwanted cells to die, the research team revealed a protein called VDAC2 was critical for the function of a key pro-death protein called Bax.
The team also showed VDAC2 contributed to the killing of certain cancer cells by anti-cancer agents. The research, published today in the journal Nature Communications, was led by PhD student Dr Hui-San Chin with Professor David Huang, Dr Mark van Delft and Associate Professor Grant Dewson.
At a glance
- The death of cells by a process called apoptosis is essential for the removal of unwanted, damaged or diseased cells, and is driven by a finely tuned protein ‘machine’.
- The protein Bax is a key component of the cell death machinery, forming part of a complex that takes cells to a ‘point of no return’ in apoptotic death.
- Our researchers discovered a protein called VDAC2 helps Bax to drive apoptosis, and may have a role in fine-tuning cancer cells’ response to anti-cancer agents.
Death machinery
Apoptotic cell death is critical for the development and maintenance of our body, and faults in the protein machinery that drives apoptosis have been linked to a range of diseases. Faulty cell death proteins have been linked to both the development of cancer, as well as resistance of cancer cells to treatment.
A key protein in the cell death machinery is called Bax, Dr van Delft said. “Bax helps to take a cell to a ‘point of no return’ when apoptotic cell death is triggered, forming pores in mitochondria, the powerhouses of the cell. This unleashes the final ‘executioner’ proteins that dismantle a cell.
new detail about a key step in cell death
“Understanding how Bax functions could lead to new therapeutics that either promote cell death – with applications for diseases such as cancer – or therapeutics that prevent cell death, which have the potential to save cells in conditions such as neurodegenerative disorders or stroke,” he said.
The team investigated how Bax and a related protein called Bak kill cells, knocking out the function of different genes using CRISPR technology, Associate Professor Dewson said.
“To our surprise we discovered a gene that was essential for the function of Bax but not Bak, despite these two proteins being functionally and structurally very similar.
“We were able to follow up on this research to show that the protein, called VDAC2, was a catalyst that helped Bax associate with mitochondria and form pores in their membranes, to kill the cell,” Associate Professor Dewson said. “Intriguingly VDAC2’s ‘day job’ is to maintain the function of the mitochondria, pumping metabolites in and out of the mitochondria.”
Our researchers discovered that the protein VDAC2 helps another protein called Bax to form pores (purple) in mitochondria when cell death is triggered. Clip taken from WEHI-TV animation 'Apoptosis and venetoclax'.
Driving cancer cell death
in driving the death of cancer cells in response to chemotherapy.
(From left) Associate Professor Grant Dewson, Professor
David Huang and Dr Mark van Delft
A failure of the cell death machinery is a hallmark of cancer cells, and is linked to the resistance of cancer cells to anti-cancer treatments, said Professor Huang.
“Bax is important for helping anti-cancer agents kill cells – without Bax and its relative Bak, cancer cells cannot undergo apoptosis when treated with a range of anti-cancer therapies.
“Our research showed that VDAC2 is required for Bax to drive the response of cancer cells to conventional chemotherapy agents as well as the recently developed BH3-mimetics,” Professor Huang said.
The research was supported by the Australian National Health and Medical Research Council, the Australian Research Council, Cancer Council Victoria, the Australian Cancer Research Foundation, the Leukaemia and Lymphoma Society (US) and the Victorian Government. Dr Hui San Chin was supported by a PhD scholarship from the University of Melbourne.
Media enquiries
M: +61 475 751 811
E: communityrelations@wehi.edu.au
Super Content:
Want to hear about our latest discoveries? Subscribe to our supporter newsletter, Illuminate.
Starting with a landmark discovery in 1988, follow the story of how Institute research has driven development of a breakthrough anti-cancer drug.
Our research has revealed the structure of a protein that triggers a form of programmed cell death called necroptosis
Institute researchers have discovered that targeting a cell ‘survival’ protein could help treat some lymphomas, including those that are resistant to existing therapies.