CCAM Seminar Series
Speaker: Dr. Meghan Driscoll, UT Southwestern
Title: “Analyzing signaling on the 3D cell surface”
Abstract: Cells regulate signaling cascades in part by controlling the localization and dynamics of signaling components via mechanisms as diverse as compartmentalization in organelles, confinement on membranes, and phase separation. The plasma membrane in particular is both a platform for carrying out the chemical reactions that comprise intracellular signaling and a conduit to the outside world. Although microscopy is vital to interrogating the spatiotemporal regulation of signaling, previous investigation was largely limited to 2D imaging despite the inherent 3D organization of the cell membrane. State-of-the-art 3D microscopy is now capable of imaging the quick and intricate undulations of cells, yet these microscopes produce large and detailed datasets that require dedicated computational workflows. To analyze 3D spatiotemporal signaling dynamics, we built a generic 3D morphological motif detector, thus enabling the analysis of signaling within these privileged morphologically-defined domains (Driscoll et al., Nat. Met., 2019). Complementing this approach, we recently developed an algorithm to measure the spatial scales of signaling organization on the 3D cell surface independent of cell morphology. To analyze the dynamics of cell surface signaling, we further developed a framework to locally track the cell surface over time by adapting the functional maps paradigm from the computer graphics field. Functional maps assign correspondences between functions painted on surfaces rather than between surfaces themselves, allowing for straightforward incorporation of biological information. Our analysis framework enables diverse applications ranging from the comparison of subcellular signaling organization across cell populations to morphological motif tracking and the measurement of spatiotemporal derivatives on the moving cell surface. Indeed, an initial version of this computational framework led to the discovery of an unexpected, new mode of 3D melanoma migration. By opening up 3D microscopy datasets to biological inquiry, our framework will propel new avenues of biological exploration.
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Speaker: Corey Acker
Title: TBA

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