Control of cell migration by mRNA targeting

The intracellular targeting of mRNAs to specific subcellular compartments enables certain proteins to be produced locally within cells. Targeted mRNA localisation is often driven by 'zipcode' sequences within the 3'UTR of transcripts, but the function of resultant local protein translation remains unclear. Using whole-genome sequencing approaches we have identified novel mRNAs that are highly enriched in the isolated lamellipodia of migrating endothelial cells, and which encode key factors controlling cell migration. Hence, targeting of mRNAs to lamellipodia by mRNA zipcodes may underpin the directional migration of endothelial cells and the formation of new blood vessels by angiogenesis. However, the in vivo functional role of targeted mRNA localisation in cell migration and tissue development has yet to be explored.

This project will define the targeting mechanisms and function of lamellipodia-specific mRNA localisation during cell migration both in vitro and in vivo. To this end, this project adopts a highly multidisciplinary approach that integrates a broad range of scientific disciplines, including in vivo bioimaging, advanced genome editing technologies, large dataset computational analyses and in vitro molecular cell biological studies. In summary, using our unique knowledge of lamellipodia-targeted mRNAs this project will:

1) Define 'zipcode' sequences responsible for driving mRNA targeting to lamellipodia.
2) Develop an in vivo model for visualisation of mRNA trafficking dynamics in vivo.
3) Probe the function of lamellipodia mRNA targeting in vitro and in vivo.