Dr. Jeremy Purvis successfully renewed his R01 grant from the National Institute of General Medical Sciences (NIGMS) for his project titled “Computational models of the human cell cycle to reveal disease mechanism and inform treatment”.
The project focuses on cell cycle plasticity—how the cell cycle adjusts to different environments. In Aim 1, the lab will combine multiplexed, single-cell imaging and stochastic modeling to determine the plasticity of cell cycle behavior in human epithelial cells and use chemical and genetic perturbations to test the physiological limits of cell cycle plasticity and refine the stochastic models to reflect the cell cycle’s inherent flexibility. Aim 2 will examine cell cycle plasticity by asking how cell cycle behavior changes during differentiation of human embryonic stem cells to the three primary germ layers: endoderm, mesoderm, and ectoderm. The team will apply a new statistical method, Spherical Principal Components Analysis (SPCA), to track changes in cell cycle behavior across each stage of embryonic development. SPCA parameters will be used to predict the molecular mechanisms coordinating cell cycle progression with stem cell differentiation. Model predictions will be tested by experimentally perturbing the activities of cell cycle regulators and assessing changes in differentiation status. Finally, Aim 3 will focus on how cell cycle behavior is influenced by non-cell-autonomous signaling mechanisms.