- 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
Gene ‘switch’ may explain DiGeorge syndrome severity
24 August 2012
found a 'switch' that modifies a gene essential for
normal heart development.
The discovery of a ‘switch’ that modifies a gene known to be essential for normal heart development could explain variations in the severity of birth defects in children with DiGeorge syndrome.
Researchers from the Walter and Eliza Hall Institute made the discovery while investigating foetal development in an animal model of DiGeorge syndrome. DiGeorge syndrome affects approximately one in 4000 babies.
Dr Anne Voss and Dr Tim Thomas led the study, with colleagues from the institute’s Development and Cancer division, published today in the journal Developmental Cell.
Dr Voss said babies with DiGeorge syndrome have a characteristic DNA mutation on chromosome 22 (22q11 – chromosome 22, long arm, band 11), but exhibit a range of mild to severe birth defects, including heart and aorta defects.
“The variation in symptoms is so prominent that even identical twins, with the exact same DNA sequence, can have remarkably different conditions,” she said. “We hypothesised that environmental factors were probably responsible for the variation, via changes to the way in which genetic material is packaged in the chromatin,” Dr Voss said.
Chromatin is the genetic material that comprises DNA and associated proteins packaged together in the cell nucleus. Chemical marks that sit on the chromatin modify it to instruct when and where to switch genes on or off, making a profound difference to normal development and cellular processes.
The research team found a protein called MOZ, the ‘switch’ which is involved in chromatin modification, was a key to explaining the range of defects seen in an animal model of DiGeorge syndrome. “MOZ is what we call an chromatin modifier, which means it is responsible for making marks on the chromatin that tell genes to switch on or off,” Dr Voss said.
“In this study, we showed that MOZ regulates the major gene, called Tbx1, in the 22q11 deletion. Tbx1 is responsible for heart and aortic arch development. In mouse models that have no Moz gene, Tbx1 does not work properly, and the embryos have similar heart and aorta defects to those seen in children with DiGeorge syndrome. We showed that MOZ is crucial for normal activity of Tbx1, and the level of MOZ activity may contribute to determining how severe the defects are in children with DiGeorge syndrome,” Dr Voss said.
Dr Voss said the study also showed that the severity of birth defects in DiGeorge syndrome could be compounded by the mother’s diet, particularly if the MOZ switch is not working properly. The research team showed that reduced MOZ activity could conspire with excess retinoic acid (a type of vitamin A) to markedly increase the frequency and severity of DiGeorge syndrome.
“In our mouse model, we saw that retinoic acid exacerbated the defects seen in mice with mutations in theMoz gene. In fact, in mice that had one normal copy of MOZ and one mutated copy, the offspring look completely normal, but if the mother’s diet was high in vitamin A, the offspring developed a DiGeorge-like syndrome. This suggests that MOZ, when coupled with a diet high in vitamin A (retinoic acid), may play a role in the development of DiGeorge syndrome in some cases.
“This interaction between the chromatin modifier MOZ, the Tbx1 gene, and retinoic acid in the diet gives a rare insight of how the environment and genetic mutations can interact at the chromatin level to cause birth defects.”
The work is supported by the National Health and Medical Research Council of Australia, British Heart Foundation, Australian Stem Cell Centre and the Victorian Government.
For further information
Liz Williams
Media and Publications Manager
Ph: +61 3 9345 2928
Mob: +61 405 279 095
Email: williams@wehi.edu.au