Double-stranded RNA (dsRNA) is a potent stimulator of innate immunity. Our immune system has evolved this response to dsRNA to signal to the body the likely presence of an invading virus – generating inflammation and recruiting immune cells. But what about all the dsRNA that our own cells produce, often as a relic of ancient viral infections, from our own genome?
My research focuses on the complex mechanisms cells need to prevent auto-inflammation against self dsRNA. Faults in these critically important pathways can result in severe and sometimes fatal auto-inflammatory diseases.
In my team, we study dsRNA regulation and a gene called ADAR1, which is an RNA editing enzyme that modifies the sequence and structure of dsRNA to prevent activation of the dsRNA immune sensor MDA5. Mutations in both ADAR1 and MDA5 result in the rare paediatric encephalopathy Aicardi-Goutières syndrome, which affects the brain, skin and immune system of children.
We use a range of cell and mouse models with ADAR1 mutations to understand the triggers of auto-inflammation, with the goal of finding new ways to intervene to prevent damaging inflammatory responses. Through genome-wide screening approaches, we have identified novel components of the inflammatory pathways triggered by self dsRNA. We study the basic biology of these regulators to better understand what they do, as well as investigating their therapeutic potential.
Applications of this research extend beyond a single disease as understanding innate immunity and inflammatory pathways is fundamental to a range of settings – from vaccines, through to cancer, viral immunity and other auto-inflammatory conditions.
Key achievements
2022 SVI Rising Star Award
2020-2023 Christine Martin Fellow, funded by 5point Foundation
2020-2022 NHMRC Ideas Grant CIA “Functions of A-to-I editing and the editing enzyme, ADAR1, in health and disease”; NHMRC Ideas Grant CIB “Defining mechanisms to prevent innate immune sensing of self-RNA”; Christine Martin Fellowship, 5point Foundation
2019 SVI Rising Star Award
2018-2019 Marian and EH Flack Fellow
2017 Susan Alberti Women in Research Award
Selected publications
AM Chalk, S Taylor, JE Heraud-Farlow*, CR Walkley* (2019) The majority of A-to-I RNA editing is not required for mammalian homeostasis. Genome biology 20 (1), 1-14
Heraud-Farlow JE, Chalk AM, Gupte, A, Taylor S, Li JB, Walkley CR (2017) Adenosine-to-Inosine RNA editing by ADAR1 is dispensable for normal murine development once self-recognition by MDA5 is prevented. Genome Biology (18) 1: 166
Liang Z, Walkley CR*, Heraud-Farlow JE* (2022) Generation of a new Adar1p150-/- mouse demonstrates isoform-specific roles in embryonic development and adult homeostasis. Biorxiv
Heraud-Farlow JE and Walkley C (2020) What do editors do? Understanding the physiological functions of A-to-I RNA editing by adenosine deaminase acting on RNAs. Open Biology 10 (7), 200085
Heraud-Farlow JE, Sharangdhar T, Li X, Pfeifer P, Tauber S, Orozco D, Hörmann A, Thomas S, Bakosova A, Farlow A, Edbauer D, Lipshitz H, Morris Q, Bilban M, Doyle M, Kiebler MA (2013) Staufen2 regulates neuronal target mRNAs. Cell Reports,5(6):1511-8
Sharangdhar T, Sugimoto Y, Heraud‐Farlow JE, Fernández‐Moya SM, Ehses J, Ruiz de los Mozos I, Ule J, Kiebler MA (2017) A retained intron in the 3′‐UTR of Calm3 mRNA mediates its Staufen2‐and activity‐dependent localization to neuronal dendrites. EMBO Rep 18(10):1762-1774
ORCID profile: https://orcid.org/0000-0002-3786-8474
Google Scholar profile: https://scholar.google.com.au/citations?user=5V4oInsAAAAJ&hl=en&oi=ao