Quantitative Cell Biology and Morphogenesis

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In animals, cells coordinate their behaviours to form, repair, or invade tissues. Collective cell movements are critical, for example, for normal embryonic development and wound healing and contribute to cancer metastasis. However, the mechanisms used by cells to coordinate their movements in living animals are not well understood. Increasing evidence indicates that, to move together, cells reorganize the molecular machinery that allows them to adhere to other cells(junctional proteins) and to generate contractile forces (cytoskeletal networks) in an attempt to increase cell cohesiveness. The mechanisms that orchestrate the molecular rearrangements that drive coordinated celll movements, however, are unclear. In addition, cells moving collectively need to be ductile to accommodate the movements of their neighbours and the complex extracellular environment in which they migrate. How cellular deformability is accomplished remains an outstanding question. Dr. Fernandez-Gonzalez and his team will use the collective cell movements that drive embryonic wound repair in fruit fly embryos to study the fundamental aspects of coordinated cell movement in vivo. Using a unique, multidisciplinary combination of live imaging, computational image analysis, and a wide array of genetic, pharmacological, and biophysical manipulations, they will investigate the mechanisms that control the reorganization of protein networks associated with coordinated cell movements, as well as the molecular cues that enable cells to change their shapes to move together efficiently. The signals that regulate cytoskeletal dynamics are conserved across species, and over 75% of genes involved in human disease exist in fruit flies. Therefore, the findings of this research program will have direct implications for the understanding of collective cell migration during embryonic development, tissue repair, and ultimately human pathology.