In this Workshop, we aim to bring together computational, cell, and evolutionary biologists to help address this major challenge of integrative cell biology. We strongly believe that actively seeking out collaboration across fields will be crucial to push cell biology beyond the boundaries of individual species into a truly comparative discipline anchored to predictive models. In turn, computational biologists will have an opportunity to guide and influence the next phase of big data generation in cell biology. Together, in deciphering the rules that underpin the relationship between the genome and the cell that encases it, we will better understand both evolution and cellular function.