Herbert Levine, Physics | NSF
DMS/NIGMS 2: Regulation of Cellular Stemness during the Epithelial-Mesenchyman Transition (EMT)
We propose a joint theoretical/experimental research program to address cell-fate trajectories that occur during induction of EMT, the epithelial-mesenchymal transition. Specifically. recent efforts have indicated that epithelial cells can either undergo direct reprogramming to mesenchymal states or alternatively become more stem-like and exhibit hybrid E/M properties. Based on our preliminary investigations, we will use state-of-the-art single cell measurement technology together with advanced mathematical modelling frameworks to understand how cells choose specific fates and to quantitatively unravel the genetic and epigenetic dynamics that leads these cells along their particular trajectories. We will develop new mathematical concepts such as the role of frustration in cell fate networks, the effects of global competition on epigenetic interactions, the role of confluency in governing cell-cell interactions, and the introduction of model-based ideas into trajectory inference, as part of our investigation.
