Centre of Research Excellence for Nucleic Acid Sensing
Nucleic acid sensing pathways are our cellular frontline defence against infection and injury, triggering a protective response.
However, errors in these pathways can lead to unwanted activation, resulting in debilitating autoinflammatory diseases. We’re advancing our fundamental knowledge of how these pathways are activated and cause disease to inform development of new therapeutic approaches.
For our immune system to function effectively it must be able to tell the difference between “self” and “non-self” molecules.
A key component of this innate defence system are sensor proteins, which monitor the cell for foreign genetic material – such as DNA or RNA from a virus. When these “non-self” nucleic acid molecules are detected in a cell, it initiates a tailored response to the virus and helps to clear the infection.
Whilst these responses protect us from pathogens, it is essential that the cell can also accurately identify and tolerate cell-derived “self” nucleic acids. We now understand that mutations in nucleic acid sensing pathways can result in inappropriate detection of “self” nucleic acids as a threat and cause significant human disease.
Diseases associated with aberrant nucleic acid sensing span a spectrum from rare inherited disorders, such as Aicardi-Goutières syndrome and systemic lupus erythematosus, through to sporadic and more common diseases such as rheumatoid arthritis and psoriasis. Currently available therapies do not adequately address patient needs, and new approaches to diagnose, treat and provide symptom relief are required.
Our Vision
This Centre of Research Excellence will focus on understanding how “self” nucleic acids can trigger common and rare inherited autoinflammatory diseases associated with mutations in nucleic acid sensing pathways. The knowledge gained of these nucleic acid sensing pathways will be crucial for the development of more selective and effective therapies for these conditions.
Chief Investigators and Program Leads
Professor Carl Walkley, Director of the CRE
Research Group Head, RNA Biology and Innate Immune Sensing, Hudson Institute of Medical Research and Monash University
Professor Seth Masters, Joint Program Leader – TLR sensing and Joint Program Leader – Therapeutics
Centre Head Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Monash University
Dr Sophia Davidson, Program Leader – DNA sensing and Neuropathologies
Research Group Head, Neuroinflammation and Neurodegeneration, Hudson Institute of Medical Research
Associate Professor Michael Gantier, Joint Program Leader – RNA sensing and Joint Program Leader – Therapeutics
Research Group Head, Nucleic Acids and Innate Immunity, Hudson Institute of Medical Research
Dr Natalia Sampaio, Joint Program Leader – RNA sensing
Research Scientist, Regulation of Interferon and Innate Signalling, Hudson Institute of Medical Research
Dr Julia Ellyard, Joint Program Leader – TLR sensing
Australian National University
Professor David Amor, Program Leader – Translation, Neurodevelopmental Disorders
Murdoch Children’s Research Institute, Royal Children’s Hospital Melbourne
Associate Investigators
Dr Dmitry Ovchinnikov, Florey Institute of Neuroscience and Mental Health
Dr Wilson Wong, Hudson Institute of Medical Research
Professor Tiong Yang Tan, Victorian Clinical Genetics Service and Murdoch Children’s Research Institute, Royal Children’s Hospital Melbourne
Professor Paul Hertzog, Hudson Institute of Medical Research
The Centre of Research Excellence for Nucleic Acid Sensing brings together a diverse and collaborative team of experts in immunology and inflammatory pathways, rare disease genetics and modelling, nucleic acid therapeutics, genetic counselling and diagnosis, management of neurodevelopmental disorders and translational science.
Our transdisciplinary themes directly address key knowledge gaps that exist in the pathology of autoimmune and autoinflammatory diseases, as we seek to define the ligands that initiate aberrant activation of inflammatory pathways, to model selected diseases in the laboratory, and then use the combined knowledge gained to generate and test new therapeutic candidates.
Research aims
Our aim is to lay the foundations to enable development of diagnostics, therapeutics and treatments for both common inflammatory disorders and rare, presently intractable diseases through:
- Greatly improved knowledge of the biology and mechanisms of aberrant nucleic acid sensing
- Implementation of novel methodologies to define the ligand triggers of nucleic acid sensing pathways, and development of novel, sensor-specific modulators
- Preclinical testing of tractable targets that can be used to reduce disease symptoms and severity and, ultimately, effectively treat diseases associated with aberrant “self” sensing.
Research underway
Identifying the nucleic acids that trigger RNA sensing pathways
Understanding diseases associated with aberrant nucleic acid sensing
Development and preclinical testing of ways to treat diseases caused by inappropriate nucleic acid sensing
Funding
The Centre of Research Excellence for Nucleic Acid Sensing is a five-year research program (01/11/2024 until 31/10/2029) funded by the National Health and Medical Research Council (NHMRC) Centres of Research Excellence program.
Collaborators
- Hudson Institute of Medical Research
- Monash University
- Australian National University
- Murdoch Children’s Research Institute
- University of Melbourne
- Victorian Clinical Genetics Service, Royal Children’s Hospital, Melbourne
- Florey Institute of Neuroscience and Mental Health, University of Melbourne
Nucleic Acid Sensing CRE
Professor Carl Walkley
Director of CRE for Nucleic Acid Sensing
Email: carl.walkley@hudson.org.au
Hudson Institute of Medical Research
27-31 Wright Street
Clayton VIC 3168