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Directed crawling motility of animal-cell types ranging from neurons to macrophages requires the coordinated force-generating activity of multiple mechanical elements. Much molecular detail is now known about the constituents of some mechanical submachines such as the polymerizing actin network and the adhesion complexes, but it is not yet clear how these elements all work together to generate coherent, directed motion at the level of the whole cell. In order to understand cellular mechanisms of large-scale coordination, the Theriot laboratory focuses on two extremely fast-moving cell types—the fish epidermal basal keratocyte responsible for the rapid closure of wounds in fish skin, and the human neutrophil that hunts down and kills microbial invaders. Despite their very different biological roles and apparent behaviors, these cells share fundamental mechanisms of self-organization and movement coordination.