Defining the spatiotemporal gene expression dynamics controlling embryonic patterning (360G-Wellcome-227415_Z_23_Z)

The ability of cells to generate complex gene expression patterns is fundamental to multicellular life. While quantitative and live imaging has transformed our understanding of transcription, recent technological advances made by ourselves and others place us on the cusp of a similar revolution in decoding mRNA stability and translation regulation. Therefore, our overarching aim is to determine how gene expression dynamics are regulated and integrated in space and time to direct embryonic cell fate decisions. We will leverage the unique advantages of the Drosophila embryo to tackle this problem. Firstly, we will combine quantitative single molecule imaging with spatiotemporal modelling to uncover transcription, mRNA stability and translation regulation at single cell resolution in the embryo. Secondly, we will dissect the mechanisms underpinning these gene expression dynamics. Thirdly, we will perturb these control mechanisms in the embryo to determine the effect on cell fate decisions. Finally, we will build a ‘digital twin’ model of the Drosophila embryo, incorporating the gene regulatory networks and their dynamics, which we will use to derive and test predictions about how embryonic patterning tolerates gene expression perturbations. Together, our data and models will reveal how the integration of spatiotemporal gene expression dynamics underpins robust embryonic patterning.