The Subcellular Transcriptome of a Dynamic Immunological Signalling Condensate

Environmental perturbations that induce a stress response in cells lead to changes in the subcellular compartmentalisation of proteins and nucleic acids. This is achieved through the formation of biomolecular condensates – organelles composed mostly of RNA and protein, that lack a surrounding membrane. 

While enormous efforts worldwide are leading to insights into the biophysics underlying condensate formation, the biological functions of condensates remain relatively understudied. We, and others, have recently observed that stimulation of immune cells results in the appearance of cytosolic biomolecular condensates containing the Retinoic acid-inducible gene (RIG)-like receptors, RIG-I and MDA5 – key molecules involved in detecting pathogens which have breached the cell wall. These novel condensates partially overlap with stress granules and their formation is dependent on functional RIG-I. 

This project will apply image-based transcriptomics at the subcellular scale, to identify changes in abundance and subcellular localisation of hundreds of transcripts in immune cells during immune stimulation. 

By visualising markers of stress granules and RIG-I condensates in the same cells, we will quantify the differential partitioning of transcripts between these different cytosolic organelles. 

This project will feeds into our groups larger efforts as we aim to understand how dynamic biomolecular condensates modulate the immune response, and how their aberrant generation contributes to autoimmune disease pathology

Lead Investigator

  • Dr Scott Berry, Group Leader School of Biomedical Sciences UNSW and EMBL Australia Node in Single Molecule Science, UNSW RNA Institute, Department of Molecular Medicine

Co-Investigator

  • Scientia Associate Professor Cecile King, Laboratory Head, School of Biotechnology and Biomolecular Medicine Sciences, UNSW