How does nuclear export shape immune responses to endogenous RNA?

• Honours
• Masters by Coursework

Self double stranded (ds)RNA potently activates the innate immune system, yet the sensors that detect it act in the cytoplasm while much self dsRNA arises in the nucleus. Nuclear export is therefore a candidate control point for inflammation. Export kinetics are known to tune innate immune gene expression (Lefaudeux, Nat Commun 2022 13(1):7197), but whether export also controls the dsRNA trigger itself is unknown.

Using functional genomics, subcellular fractionation and imaging, we are defining how the export machinery delivers self dsRNA to sensors, separating effects on the trigger from downstream interferon output. Building on the lab’s recent publication (Heraud-Farlow, Sci Immunol 2024 9(101):eadk0412), the student will map dsRNA localisation and immune activation, gaining skills in RNA biology, subcellular fractionation, RNA imaging, CRISPR and RNA-seq.

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.