Role of novel surface glycosylated RNA molecules (glycoRNA) in infection biology

The cell surface glycocalyx is a complex and dynamic structure formed by proteins and lipids bound to the plasma membrane. These are usually glycosylated (glycoproteins and glycolipids, and play important roles in cell physiology but also in infection biology as interactive receptors for pathogens or defence molecules. Recently in 2021, a new type of cell surface molecule has been discovered, formed by a main RNA body modified by the addition of a glycan, and hence named glycoRNA. To date, the biological functions of glycoRNA remain unknown. This project aims at elucidating the role of glycoRNAs in infection using multiple viral (e.g., SARS-CoV-2, dengue, Zika virus) and parasitic (Trypanosoma, Leishmania, Plasmodium, filarial parasites) infection systems. The project will identify potential roles of glycoRNA in pathogen interaction, attachment and/or invasion of host cells, as well as changes in glycoRNA composition and abundance induced by infection, with the ultimate goal of exploiting glycoRNAs to develop new therapeutic strategies to tackle infection. This highly interdisciplinary project requires advanced cell and molecular biology methods to edit and knock out host glycoRNA genes using CRISPR-Cas9/13, as well as virus/parasite genome editing, and metabolic labelling and click/bioorthogonal chemistry to label glycoRNA for its detection using blotting-based methods. It also involves state-of-the-art confocal and high content microscopy to image glycoRNA using immunostaining and aptamer and RNA in situ hybridization-mediated proximity ligation assay (ARPLA), and the use of transcriptomics and glycomics to fully identify and characterise glycoRNAs. In summary, the study of glycoRNA presents a huge potential for basic and translational discoveries in infection biology