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The Clinical Immunogenomics Research Consortium Australasia

microscope image showing different colour cells

CIRCA is a research collaboration that brings together experts across different specialties, from scientific and research organisations globally, to identify the causes of challenging immune diseases. CIRCA creates research opportunities through an established ecosystem of scientists and clinicians from many disciplines, to accelerate the discovery and diagnosis of rare immune diseases.

CIRCA is based at the Garvan Institute of Medical Research, within the St Vincent’s Sydney Health Innovation Precinct. This advantageous physical proximity to immense research expertise supports CIRCA’s collaborative ecosystem ideology. Easy access to diverse collaborators and cutting-edge platform technologies creates synergistic opportunities for CIRCA’s research projects and participants. CIRCA’s goal is to understand the molecular and cellular mechanisms causing immunological diseases by creating a virtual network of expert clinicians, researchers and technologies, to deliver faster diagnoses to families and contribute significantly to the progress of immunogenomic research.

People with rare, extreme conditions of immune dysregulation may find it difficult to obtain a diagnosis through traditional clinical testing methods. For these people, undergoing genetic testing or genome sequencing may make it possible to obtain a genetic diagnosis  - identification of the genetic variant that underpins their disease. A genetic diagnosis potentially allows a patient to receive precision treatment specifically tailored to them and to anticipate future outcomes for their prognosis. It can also end the ‘diagnostic odyssey’ of invasive, inconclusive testing. CIRCA aspires to improve the healthcare for these patients by translating science into improved outcomes.

CIRCA was launched in 2015 to improve the lives of patients living with rare immune diseases. By using next-generation sequencing, it aims to diagnose and accelerate our understanding of these conditions and to facilitate the discovery of targeted therapies. It was Australia’s first integrated clinical program in immunogenomics and was founded with 32 initial members drawn from major teaching hospitals, universities and research institutes from across the Greater Sydney area. Since 2017, with funding from the Jeffrey Modell Foundation (USA), we have expanded our reach to centres across Australia and New Zealand.

Since its launch in 2015, CIRCA has:

  • Achieved world-class standards of diagnostic rates
  • Earned a reputation of high regard through consistent, high-quality publications
  • Attracted commercial and international partnerships
  • Created a community of 200+ members from 10+ research facilities across Australia and 40+ approved or in progress recruitment sites servicing Victoria, South Australia, New South Wales, Western Australia, Queensland and New Zealand.

Our key aims

1Accelerate the discovery and diagnosis of rare immune diseases

CIRCA creates infrastructure and support for clinicians and scientists to optimally pursue discoveries. For example, CIRCA has expanded its ethics and governance remit and is continuously increasing its reach across Australia. We work towards equitable access for all patients across Australia.

2Improve treatment pathways and clinical practice for immune diseases

CIRCA works closely with clinicians and collaborators to support the clinical environment with scientific facts and discoveries. The work we do on mechanisms of disease assists clinicians in their work to access pharmaceuticals for patients and impact management and treatment decisions.

3Build global research opportunities for our community

CIRCA has a well-established ecosystem or community of like-minded multidisciplinary experts who are invested in finding the diagnosis and discovery of immunogenomic diseases. CIRCA facilitates forums and symposiums for discussion and education, breaking down traditional silos for the benefit of the patient.

Our partners

CIRCA has been supported by the NSW Office of Health and Medical Research, the Bill and Patricia Ritchie Foundation, the Jeffrey Modell Foundation (USA), Costco, the National Health and Medical Research Council of Australia, CORIO, the John Brown Cook Foundation and the Allergy and Immunology Foundation of Australia (AIFA).

Collaborators, industry partners and sponsors:

  • Allergy and Immunology Foundation of Australia (AIFA)
  • St Vincent’s Centre for Applied Medical Research (AMR) 
  • Centre for Population Genomics (CPG)
  • CSL 
  • Immune Deficiencies Foundation of Australia (IDFA)
  • Invitae
  • John Brown Cook Foundation  
  • Kinghorn Centre for Clinical Genomics 
  • NSW Health Pathology 
  • SydPath 

International collaborators

  • Jean Laurent Casanova, Rockefeller University, NY USA; Imagine Institut Paris, France
  • Isabelle Meyts, Katholic University, Leuven, Belgium
  • Gulbu Uzel, National Institute of Allergy and Infectious Disease, National Institute of Health, Bethesda, MD USA
  • Dr Steve Holland, National Institute of Allergy and Infectious Disease, National Institute of Health, Bethesda, MD USA

Lists of sites

CIRCA has approved sites in the following states in Australia:

  • New South Wales
  • Queensland
  • Victoria
  • Western Australia

We strive to offer equitable access to our skills and aim to have a presence in every state and territory as soon as we are permitted.

At CIRCA, we work closely with scientists and clinicians to facilitate easy access to genomic and functional testing and access to our network of global expertise partners. CIRCA’s established infrastructure was built to support the discovery of genomic causes of immune disease and to facilitate investigator-lead projects within the CIRCA Study remit.

By providing access to state-of-the-art functional and genomics research expertise, CIRCA brings together a multidisciplinary collaborative team to understand the clinical manifestations in families with rare or novel pathogenic gene variants that cause Primary Immune Deficiencies (PIDs) or Inborn Errors of Immunity (IEI). This has allowed for improved understanding and treatment of both the rare diseases underpinned by these genetic variations, as well as common immunological diseases in which the same pathways are involved.

The identification of genetic variants as a diagnostic tool not only brings an end to invasive and often inconclusive testing, but it also allows clinicians to tailor treatments to individual patients. Increasingly, cellular techniques and other translational tools, such as RNAseq and single cell transcriptomics, are used to understand the mechanisms of disease or validate diagnoses. By understanding the mechanisms and pathways of disease, we can improve therapeutics and patient care for all.

CIRCA’s primary activities are:

  • Providing state-of-the-art genetics, genomics and DNA/RNA sequencing techniques to understand the cause of disease in patients with rare or novel gene mutations.
  • Functional testing of the immune system through partnerships with local and global laboratories.
  • Hosting regular multidisciplinary forums for clinicians and scientists to discuss difficult-to-diagnose cases and receive support.
  • Facilitating investigator-led projects through an established ethics and governance framework and operational infrastructure.
  • Creating research opportunities through an extensive global network of collaborating scientists and clinicians to accelerate discovery and diagnosis of rare immune diseases
  • Building a de-identified phenotype-genotype database of rare disease patents with biobanked bloods samples and whole genome sequence data.

CIRCA Steering Committee  

  • Professor Stuart Tangye (Chairperson): Laboratory Head | Immunology and Immunodeficiency, Garvan
  • Dr Paul Gray (Vice-Chairperson): Immunologist and Pathologist, Sydney Children’s Hospital and Campbeltown Hospital
  • Rebecca MacIntosh: Genetic Counsellor, Sydney Children’s Hospital
  • Christine Jeffery: Vice Chair IPOPI; Past CEO, IDFA; Patient Advocate
  • Dr Alisa Kane Immunologist and Pathologist, St Vincent’s Hospital and Liverpool Hospital
  • Professor  Leslie Burnett: Genomic Pathologist; Garvan and Invitae
  • Assoc Professor Elissa Deenick: Laboratory Head | Immunology and Immunodeficiency, Garvan
  • Dr Karen Enthoven: Project Manager, CIRCA
  • Dr Melanie Wong: Immunologist and Pathologist, Children’s Hospital Westmead

Project Management Team

  • Dr Karen Enthoven: Project Manager, CIRCA
  • Patrick O’Young, Research Assistant, CIRCA

Research Team

  • Dr Georgina Hollway
  • Assoc Professor Elissa Deenick
  • Professor Stuart Tangye
  • Assoc Professor Cindy Ma Laboratory Head | Immunology and Immunodeficiency, Garvan
  • Dr Karen Enthoven
  • Patrick O’Young

Case Review Team

  • Dr Ming-Wei Lin, Immunologist, Westmead Hospital
  • Dr Peter McNaughton Immunologist, Children’s Health Queensland
  • Dr Peter Hsu Immunologist, Children’s Hospital Westmead
  • Dr Melanie Wong Immunologist, Children’s Hospital Westmead
  • Anne Sullivan Nurse, Children’s Health Queensland
  • Dr Pei Dai, Postdoctoral and Immunologist, St Vincent’s
  • Dr Paul Grey
  • Professor Stuart Tangye
  • Professor Leslie Burnett

VUS Club

  • Professor Leslie Burnett
  • Rebecca McIntosh
  • Dr Paul Gray

Data Access Committee

  • Mary-Anne Young
  • Joe Copty
  • Professor Stuart Tangye
  • Matthew Hobbs
  • Professor Leslie Burnett
  • Professor Tri Phan

Selected Publications

See all publications
  • 2018
    The Journal of experimental medicine10.1084/jem.20180010

    Germline-activating mutations in compromise B cell development and function.

    Danielle T Avery, Alisa Kane, Tina Nguyen, Anthony Lau, Akira Nguyen, Helen Lenthall, Kathryn Payne, Wei Shi, Henry Brigden, Elise French, Julia Bier, Jana R Hermes, David Zahra, William A Sewell, Danyal Butt, Michael Elliott, Kaan Boztug, Isabelle Meyts, Sharon Choo, Peter Hsu, Melanie Wong, Lucinda J Berglund, Paul Gray, Michael O'Sullivan, Theresa Cole, Steven M Holland, Cindy S Ma, Christoph Burkhart, Lynn M Corcoran, Tri Giang Phan, Robert Brink, Gulbu Uzel, Elissa K Deenick, Stuart G Tangye
  • 2018
    Science immunology10.1126/sciimmunol.aat4956

    A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity.

    Vivien Béziat, Juan Li, Jian-Xin Lin, Cindy S Ma, Peng Li, Aziz Bousfiha, Isabelle Pellier, Samaneh Zoghi, Safa Baris, Sevgi Keles, Paul Gray, Ning Du, Yi Wang, Yoann Zerbib, Romain Lévy, Thibaut Leclercq, Frédégonde About, Ai Ing Lim, Geetha Rao, Kathryn Payne, Simon J Pelham, Danielle T Avery, Elissa K Deenick, Bethany Pillay, Janet Chou, Romain Guery, Aziz Belkadi, Antoine Guérin, Mélanie Migaud, Vimel Rattina, Fatima Ailal, Ibtihal Benhsaien, Matthieu Bouaziz, Tanwir Habib, Damien Chaussabel, Nico Marr, Jamel El-Benna, Bodo Grimbacher, Orli Wargon, Jacinta Bustamante, Bertrand Boisson, Ingrid Müller-Fleckenstein, Bernhard Fleckenstein, Marie-Olivia Chandesris, Matthias Titeux, Sylvie Fraitag, Marie-Alexandra Alyanakian, Marianne Leruez-Ville, Capucine Picard, Isabelle Meyts, James P Di Santo, Alain Hovnanian, Ayper Somer, Ahmet Ozen, Nima Rezaei, Talal A Chatila, Laurent Abel, Warren J Leonard, Stuart G Tangye, Anne Puel, Jean-Laurent Casanova
  • 2019
    The Journal of allergy and clinical immunology10.1016/j.jaci.2019.01.033

    Activating mutations in PIK3CD disrupt the differentiation and function of human and murine CD4 T cells.

    Julia Bier, Geetha Rao, Kathryn Payne, Henry Brigden, Elise French, Simon J Pelham, Anthony Lau, Helen Lenthall, Emily S J Edwards, Joanne M Smart, Theresa S Cole, Sharon Choo, Avni Y Joshi, Roshini S Abraham, Michael O'Sullivan, Kaan Boztug, Isabelle Meyts, Paul E Gray, Lucinda J Berglund, Peter Hsu, Melanie Wong, Steven M Holland, Luigi D Notarangelo, Gulbu Uzel, Cindy S Ma, Robert Brink, Stuart G Tangye, Elissa K Deenick
  • 2019
    Journal of clinical immunology10.1007/s10875-019-00646-z

    Autoinflammation Masquerading as Autoimmunity in an Adult with Heterozygous p.E250K PSTPIP1 Mutation.

    Pei Dai, Tim Furlong, Gary Gracie, Min Li Huang, Tao Yang, Kathy H C Wu, Mark Danta, Melanie Wong, Andrew Williams, Lyn March, Marie Hetherington, David Heyworth-Smith, Tri Giang Phan
  • 2018
    Journal of clinical immunology10.1007/s10875-018-0477-z

    Reversible Suppression of Lymphoproliferation and Thrombocytopenia with Rapamycin in a Patient with Common Variable Immunodeficiency.

    Elissa K Deenick, Adrienne Morey, Mark Danta, Louise Emmett, Keith Fay, Gary Gracie, Cindy S Ma, Rebecca Macintosh, Sandy A B C Smith, Sarah C Sasson, William A Sewell, Mark Cowley, Stuart G Tangye, Anthony D Kelleher, , Tri G Phan


If you or a family member has a rare immunodeficiency with no current genetic diagnosis, please speak to your clinical immunologist about the possibility of participating in CIRCA.


If you wish to be involved or have patients you'd like to be considered for inclusion in a CIRCA study, please email:  


Interested scientific researchers can email: