Understanding subcellular RNA localisation in blood vessel growth and homeostasis

Subcellular mRNA localisation regulates multiple biological processes, from neuronal plasticity and cell migration to acquisition of cell fates. Although the asymmetric distribution of mRNAs has now been reported in multiple cell types, precise mechanisms of mRNA localisation and the consequent implications for tissue formation, maintenance and homeostasis are less understood. Preliminary data showed that proteins classically known for their roles as actin adaptors can bind RNAs in endothelial cells, hinting towards a potential link between cytoskeletal reorganisation and mRNA distribution. Together with the support of robust collaborations, we will develop an innovative experimental programme demonstrating the relevance of spatial control of gene expression for complex biological systems. Firstly, we aim to investigate how actin-binding proteins regulate subcellular mRNA localisation and local translation in the context of endothelial cell motility and blood vessel formation. Secondly, we will uncover novel RNA-protein interactions during endothelial barrier disruption and study the impact of asymmetric mRNA distribution in endothelial cell-cell junction during vessel remodelling. Finally, using murine models of retinal vascular development, we will explore in vivo roles of mRNA localisation. Altogether, our work will expose how unappreciated mechanisms underpinning subcellular mRNA compartmentalization shapes mechanisms of tissue biology.