- 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
- Partnering opportunities
- A complete cure for HBV
- A stable efficacious Toxoplasma vaccine
- Activating SMCHD1 to treat FSHD
- Improving vision outcomes in retinal detachment
- Intercepting inflammation with RIPK2 inhibitors
- Novel inhibitors for the treatment of lupus
- Novel malaria vaccine
- Precision epigenetics silencing SMCHD1 to treat Prader Willi Syndrome
- Rethinking CD52 a therapy for autoimmune disease
- Targeting minor class splicing
- Royalties distribution
- Start-up companies
- Partnering opportunities
- Collaborators
- Publications repository
- Awards
- Discoveries
- Centenary 2015
- History
- Contact us
- Research
- Diseases
- Cancer
- Development and ageing
- Immune health and infection
- Research fields
- Research technologies
- People
- Anne-Laure Puaux
- 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 Emma Josefsson
- Associate Professor Ethan Goddard-Borger
- Associate Professor Grant Dewson
- Associate Professor Isabelle Lucet
- Associate Professor James Murphy
- Associate Professor James Vince
- Associate Professor Jason Tye-Din
- Associate Professor Jeanne Tie
- Associate Professor Jeff Babon
- Associate Professor Joan Heath
- Associate Professor Justin Boddey
- Associate Professor Kate Sutherland
- Associate Professor Leanne Robinson
- Associate Professor Marco Herold Marco Herold
- Associate Professor Marie-Liesse Asselin-Labat
- Associate Professor Matthew Ritchie
- 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 Sant-Rayn Pasricha
- Associate Professor Seth Masters
- Associate Professor Sumitra Ananda
- Associate Professor Tim Thomas
- Associate Professor Wai-Hong Tham
- Associate Professor Wei Shi
- Catherine Parker
- Chela Niall
- Deborah Carr
- Dr Alisa Glukhova
- Dr Anna Coussens
- Dr Ashley Ng
- Dr Ben Tran
- Dr Bernhard Lechtenberg
- Dr Brad Sleebs
- Dr Drew Berry
- Dr Gemma Kelly
- Dr Gwo Yaw Ho
- Dr Hui-Li Wong
- Dr Jacqui Gulbis
- Dr Joanna Groom
- Dr John Wentworth
- Dr Kelly Rogers
- Dr Lucy Gately
- Dr Margaret Lee
- Dr Mary Ann Anderson
- Dr Maryam Rashidi
- Dr Matthew Call
- Dr Melissa Call
- Dr Philippe Bouillet
- Dr Rebecca Feltham
- Dr Samir Taoudi
- Dr Shalin Naik
- Dr Sheau Wen Lok
- Dr Simon Chatfield
- Dr Tracy Putoczki
- Guillaume Lessene
- Helene Martin
- Joh Kirby
- Kaye Wycherley
- Keely Bumsted O'Brien
- Mr Joel Chibert
- 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 Gabrielle Belz
- Professor Geoff Lindeman
- Professor Gordon Smyth
- Professor Ian Wicks
- Professor Ivo Mueller
- Professor Jane Visvader
- Professor Jerry Adams
- Professor John Silke
- Professor Ken Shortman
- Professor Leonard C Harrison
- Professor Lynn Corcoran
- Professor Marc Pellegrini
- Professor Marnie Blewitt
- Professor Melanie Bahlo
- Professor Mike Lawrence
- Professor Nicos Nicola
- Professor Peter Colman
- Professor Peter Gibbs
- Professor Phil Hodgkin
- Professor Stephen Nutt
- Professor Suzanne Cory
- Professor Terry Speed
- Professor Tony Burgess
- Professor Tony Papenfuss
- Professor Warren Alexander
- Diseases
- Education
- PhD
- Honours
- Masters
- Undergraduate
- Student research projects
- A new regulator of stemness to create dendritic cell factories for immunotherapy
- Advanced methods for genomic rearrangement detection
- Control of cytokine signaling by SOCS1
- Defining the protein modifications associated with respiratory disease
- Delineating the pathways driving cancer development and therapy resistance
- Developing a new drug that targets plasmacytoid dendritic cells for the treatment of lupus
- Development and mechanism of action of novel antimalarials
- Development of a novel particle-based malaria vaccine
- Development of tau-specific therapeutic and diagnostic antibodies
- Discovering novel therapies for major human pathogens
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Epigenetic biomarkers of tuberculosis infection
- Essential role of glycobiology in malaria parasites
- Evolution of haematopoiesis in vertebrates
- Human lung protective immunity to tuberculosis
- Identifying novel treatment options for ovarian carcinosarcoma
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of mutant p53 in cancer
- Microbiome strain-level analysis using long read sequencing
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Modelling spatial and demographic heterogeneity of malaria transmission risk
- Naturally acquired immune response to malaria parasites
- Predicting the effect of non-coding structural variants in cancer
- Structural basis of catenin-independent Wnt signalling
- Structure and biology of proteins essential for Toxoplasma parasite invasion
- T lymphocytes: how memories are made
- TICKER: A cell history recorder for longitudinal patient monitoring
- Targeting host pathways to develop new broad-spectrum antiviral drugs
- Targeting post-translational modifications to disrupting the function of secreted proteins
- Targeting the epigenome to rewire pro-allergic T cells
- Targeting the immune microenvironment to treat KRAS-mutant adenocarcinoma
- The E3 ubiquitin ligase Parkin and mitophagy in Parkinson’s disease
- The molecular controls on dendritic cell development
- Understanding malaria infection dynamics
- Understanding the genetics of neutrophil maturation
- Understanding the neuroimmune regulation of innate immunity
- Understanding the proteins that regulate programmed cell death at the molecular level
- Using cutting-edge single cell tools to understand the origins of cancer
- When healthy cells turn bad: how immune responses can transition to lymphoma
- 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
- 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
'Mix and match' assembly instructions guide immune cell attacks
5 September 2017
have discovered a unique set of ‘assembly instructions’ for
receptors that guide immune cell attack.
Institute researchers have discovered how immune cells use a unique set of assembly instructions to ‘mix and match’ how they respond to, and kill, tumour and diseased cells.
Cell surface receptor complexes are like Lego pieces, constructed using different molecular combinations to guide how the immune cell acts when it makes contact with a cancerous cell, an infection, or other external signals. The new research identifies the features that allow these pieces to assemble in specific combinations.
Understanding how these complexes assemble ‘naturally’ could pave the way for future improvements in immunotherapy, such as engineering cancer-specific immune killers.
Associate Professor Matthew Call and Dr Melissa Call from the Walter and Eliza Hall Institute led the research with colleagues in Spain and the US, published in the journal Proceedings of the National Academy of Sciences.
Associate Professor Matthew Call said the team discovered an entirely new set of assembly instructions used by molecular sensors embedded in the thin fatty cell membrane to build receptor complexes in response to different stimuli.
“Effectively, these membrane-bound sensors determine ‘who’ the immune cell talks to. This is really important in the promising field of cancer immunotherapy, because it could help us better engineer cells to specifically talk to – and destroy – cancer cells,” Associate Professor Matthew Call said.
Cell surface receptor complexes consist of an external receptor that binds to signalling molecules, an internal molecule that instructs the cell how to respond, and a cell membrane-embedded portion that anchors and links the other two segments.
In the past, these cell membrane-embedded sections of the receptor were largely ignored, partly because they are so difficult to work with, Associate Professor Matthew Call said.
“However more and more we are discovering what a critical role they play in how signals are received and acted upon by the cell. In fact, the sensors found in the fatty cell membrane actually control how the cell responds to external signals by pulling different external and internal sections together like building blocks to drive the correct response,” he said.
The researchers began by studying the receptors on natural killer (NK) cells, but found that the same assembly instructions were used in a host of immune cells that “run around and eat and blow up” cancerous and other diseased cells, Dr Melissa Call said.
“One subset of these receptors, called Fc receptors, were the focus of this research. We were particularly looking at the subset of Fc receptors found on natural killer (NK) cells – immune cells that poison tumour and virus-infected cells that have been ‘marked’ by antibodies,” Dr Melissa Call said.
She said the study showed that different subsets of Fc receptors used completely different assembly instructions compared to other, similar receptors.
“Over the past decade or so, this has become really important therapeutically because of a new field of cancer immunotherapy called chimeric antigenic receptor therapy, or CART,” Dr Melissa Call said.
“The idea of CART is that you create specially engineered receptors in immune cells that are highly specific for an individual cancer. Understanding in depth how these receptors are assembled naturally is vital for us to understand how best to design them ourselves for cancer therapy, to look at improved ways of stimulating the immune response to cancer.”
Dr Melissa Call said the laboratory’s long-term goal was to decipher and control how immune receptors work, to find new ways of manipulating the immune response for therapeutic treatments.
“Controlling how the immune receptors are assembled could allow us to boost the immune response in the case of infections or immune deficiencies, dampen it down in the case of autoimmune disease, or redirect the immune response to better target cancers,” she said.
The research was supported by the Australian Research Council 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.