How is host double-stranded RNA regulated to prevent autoinflammation?

• Honours
• Masters by Coursework
• PhD

Pathogen or host-derived double stranded (ds)RNA is a potent activator of the innate immune system, eliciting a strong inflammatory response. Host dsRNA is transcribed, exported, localised and degraded, with loss of homeostasis at any stage driving inflammation. Using unbiased CRISPR screens and functional genomics, we are identifying the genes that determine intracellular dsRNA levels, asking how dsRNA is transported between compartments, and dissecting how it is turned over.

Having recently identified new regulators of the dsRNA response (Heraud-Farlow, Sci Immunol 2024 9(101):eadk0412), we combine biochemistry, cell biology and functional genomics to define how each protein interacts with dsRNA and how its loss reshapes inflammation. Students will characterise these regulators, gaining hands-on skills in RNA biology, cell culture, CRISPR, RNA-seq, RNA-protein interactions, FACS and microscopy.

This project is open to students in the CareerTracker and Metcalf Scholarship programs.

The mission of the Heraud-Farlow lab, a newly established group, is to understand how cells regulate double-stranded RNA (dsRNA) and dsRNA sensing, and to translate that understanding into new therapies for inflammatory disease and safer RNA-based medicines. We work at the interface of RNA biology and innate immunity, combining cellular and molecular biology, functional genomics and patient-derived disease models.

We aim to define the rules that govern dsRNA recognition, identify new therapeutic targets in the dsRNA-sensing pathway, and develop RNA-based approaches to reset inflammation. This work spans rare monogenic conditions, such as Aicardi-Goutières syndrome, and the growing number of common inflammatory diseases now linked to dsRNA dysregulation. As a new lab, we are committed to building a supportive, inclusive learning environment for students.