- 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 Jeanne Tie
- 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 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 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 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 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
- 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
- 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
- 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
- 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
- Statistical analysis of single-cell multi-omics data
- Structural and functional analysis of epigenetic multi-protein complexes in genome regulation
- 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
- 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 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
'Missing link' explains how viruses trigger immunity
12 September 2017
A discovery by Melbourne researchers has solved a longstanding mystery of how viruses trigger protective immunity within our body.
mystery of how viruses trigger protective immunity.
The research team demonstrated a protein called SIDT2 was crucial for cells to detect viral components in their environment, and initiate an immune response to reduce the virus’ spread.
As well as being an important part of the intricate ‘arms race’ between viruses and our immune system, the finding could inform better approaches to delivering a promising new class of therapeutics.
The study was led by Dr Tan Nguyen, Dr Ken Pang, Associate Professor Seth Masters and Professor Ian Wicks at the Walter and Eliza Hall Institute, together with Dr Michelle Tate at the Hudson Institute of Medical Research, and Professor Craig Hunter at Harvard School, US. The research was published today in the journal Immunity.
During a viral infection, RNA – a genetic material similar to DNA – is released into the environment around the infected cells. Dr Nguyen said the team showed that SIDT2 allowed viral RNA to be shuttled between compartments within cells, allowing it to reach the proteins that trigger anti-viral immunity.
“This RNA is in a ‘double-stranded’ form, called ‘dsRNA’, that is not normally found in our body. Human cells have evolved ways to detect dsRNA as a warning sign of an active viral infection and, in this way, dsRNA acts as an important trigger for cells to mount an anti-viral immune response.
“Cells constantly survey their environment by ‘swallowing’ small samples of their environment into compartments called endosomes. The enigma was that no one knew how the dsRNA escaped the endosome to reach the cytoplasm, where it can be detected by the cell.” Dr Nguyen said.
The team showed that SIDT2 was the crucial missing link needed to transport dsRNA out of endosomes, and enable an immune response to be launched.
Viruses have many strategies to prevent an infected cell from alerting the immune system to their presence, Dr Pang said. “Intriguingly, we showed that SIDT2 is critical for uninfected ‘bystander’ cells to detect viral RNA in their environment,” Dr Pang said. “This means bystanders can trigger protective immunity before they even encounter the virus itself.
“Viruses have evolved many ways to switch off the immune response, allowing them to spread, while humans have evolved counter measures to allow a rapid and protective immune response that contains the viral infection. SIDT2 is helping humans in the ‘arms race’ between viruses and their human hosts.”
The research may also have future implications for a new class of therapeutics based on dsRNA.
“For more than a decade there have been attempts to use modified dsRNA to switch off genes that cause disease – an approach called RNA interference,” Dr Pang said.
“While there have been many clinical trials utilising RNA interference, delivering RNA into cells has been a huge challenge and the lack of effective delivery has meant that these trials have all ultimately failed.
“Now that we know SIDT2 is important in trafficking double-stranded RNA into cells, future RNA-based therapeutics can hopefully be designed to maximise their transport by SIDT2,” Dr Pang said.
Dr Nguyen undertook the research as a PhD student at the Institute enrolled through the University of Melbourne. Dr Pang now works at the Murdoch Children’s Research Institute.
The research was supported by the Australian National Health and Medical Research Council, the Royal Australasian College of Physicians, the Menzies Foundation, the CASS Foundation, the John T Reid Charitable Trusts, Sylvia & Charles Viertel Senior Medical Research Fellowship, the US National Institutes of Health and the Victorian Government Operational Infrastructure Support Program.
Media enquiries
M: 0475 751 811
E: communityrelations@wehi.edu.au
Super Content:
Want to hear about our latest discoveries? Subscribe to our supporter newsletter, Illuminate.