Investigating the mechanisms underlying collective migration of heterogeneous groups of cells during tissue morphogenesis and cancer metastasis

Embryonic development requires the precise spatio-temporal activation of specific cell behaviours such as migration and division. Re-activation of these processes in adult cells is a hallmark of cancer. This makes experimental models for studying developmental processes, such as the fruit fly Drosophila melanogaster, highly informative for cancer studies: such research has often provided the first glimpse into the mechanism of action of human cancer-related proteins. In our lab, we use Drosophila to study the basic biology of epithelial-to-mesenchymal transitions (EMTs), as well as the collective migration of heterogenous cell populations, which results from partial-EMTs. We study these processes during normal development of the embryonic midgut, and also during tumour progression in an exciting newà  model of metastatic colorectal cancer that we recently generated.à  The collective migration of the embryonic midgut cells during Drosophila development is a particularly fascinating model for collective migration, as the midgut constitutes a mixed population of epithelial-like, mesenchymal and progenitor cells, yet midgut migration is highly coordinated both within and between these different cell types. Using the midgut as a paradigm, ongoing research in the lab is focused on identifying the mechanisms and mechanics of heterogeneous collective cell migration. Until recently, the study of midgut migration was restricted to simple qualitative analysis in fixed embryos, preventing quantification of cell-to-tissue scale behaviour. We recently pioneered live-imaging of midgut migration, enabled by multi-photon confocal microscopy, and have developed methods to perform 4-D tracking of the different cell populations within the migrating midgut. This has already allowed us to extract quantitative parameters and identify a novel role for E-cadherin mediating adhesion during cell migration. With our studies moving from qualitative descriptions to state-of-the-art deep-tissue imaging, quantitative analysis and generation of complex datasets, there is a pressing need to combine these innovative approaches with biophysical and computational modelling techniques, which we currently need help in developing.Non UBCUnreviewedAuthor affiliation: University of SheffieldResearche