Modelling wound re-epithelialisation in the Drosophila embryo (360G-Wellcome-089627_Z_09_Z)

The main focus of my investigation will be to study the molecular mechanisms behind epithelial sheet contact inhibition of migration and subsequent fusion. The Drosophila embryo wound healing model is an efficient way to study in vivo wound healing, and with many signalling events seemingly conserved across phyla to mammalian wound healing, in the future we hope to translate interesting findings into more complex and clinically relevant models. Our studies will involve live imaging Drosophila embryo wound healing in vivo using confocal microscopy. For this, I will collect stage 15 embryos expressing various key proteins fused to fluorescent reporters in the epidermis; I will wound the embryos on the ventral epithelial surface using laser ablation, as previously described, and image for 3 hours capturing the interaction of epithelial fronts as the wound seals closed. With this method I will: I. Characterise 'the steps of contact inhibition as migrating epithelial cell sheets contact and fuse to one another; in particular, I will live image actin and microtubule dynamics and calcium signals during wound re-epithelialisation and fusion; 2. Investigate epigenetic regulation of wound re-epithelialisation; 3. Reveal mechanical signals during wound closure and determine how they influence wound re-epithelialisation.