Intrinsic and environmental influences on thymocyte migration signatures

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Cell migration is important for a number of biological processes including cell and tissue development. The behavior of migrating cells is incredibly diverse: some cells migrate slowly and others fast, some cells travel along a fairly straight path to a specific destination while others migrate tortuously with no obvious directionality, and some migrate individually whereas others move as a group. Why certain migration patterns are associated with particular cell types and what factors influence these migration signatures is not well described for many cell subsets. As a model to address these biological questions, we study the migration patterns of a subtype of immune cells called T cells as they develop in the thymus. The progenitor cells that seed the thymus transit through a series of well-characterized developmental intermediates, and thymocytes (immature T cells) at each stage of development display distinct migration signatures. During one developmental transition in particular, thymocytes more than double their speed transitioning from slow, meandering cells into cells that move with increased straightness and become among the fastest cells in the body. These developmental stages occur in distinct locations in the thymus, but the factors that influence their migratory signatures are not well described. We use a unique organ culture system and advanced microscopy techniques to visualize the dynamic migration of developing T cells in intact thymus tissue in order to identify the factors that influence migration patterns and determine how modulating these movements influence T cell development. In addition, we apply image analyses and machine learning approaches to identify cell subsets within a heterogeneous population based on their migration signature in intact tissue. Ultimately, these studies will contribute to our understanding of how cell migration is optimized for proper development and function of developing T cells, other immune cells, and beyond. Further, in the context of this research program several undergraduate and graduate students will receive interdisciplinary training using state-of-the-art technologies that will equip them with the skills they need to excel in the burgeoning fields of immunology and biophotonics in Canada.