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This Teaching Resource provides lecture notes, slides, and a student assignment for a two-part lecture on mathematical modeling using the Virtual Cell environment. The lectures discuss the steps involved in developing and running simulations using Virtual Cell, with particular focus on spatial partial differential equation models. We discuss how to construct both ordinary differential equation models, in which the cytoplasm is considered a well-mixed cellular compartment, and partial differential equation models, which calculate how chemical species change as a function of both time and location. The Virtual Cell environment is especially well suited for models that explore spatial specificity of cellular reactions. Partial differential equation models in Virtual Cell can give rise to simulations using predefined cellular geometries, which enable direct comparison with imaging data. These models address questions regarding the regulatory capability arising from spatial organization of the cell. Examples are provided of studies that have successfully exploited the Virtual Cell software to address the spatial contribution to signaling.