Minimal frustration in the regulation of cell-fate choice
Abstract: Multi-cellular organisms are composed of a variety of cell types, all arising from a single cell. The choice between different cell fates during development and during processes such as wound healing and immune response is mediated by gene regulatory networks, with each cell fate characterized by a specific gene expression pattern. Identifying features of gene networks that allow for the establishment and maintenance of cell type-specific expression patterns is key to understanding the mechanisms underlying cell-fate choice and how this process can go awry in a disease like cancer. In this talk, I will introduce minimal frustration― broadly defined as the absence of conflicting regulatory relationships― as a fundamental property characterizing a variety of biological networks. The minimal frustration property, absent in random networks with similar topological properties, is crucial to the ability of gene regulatory networks to robustly establish and maintain cell types. More generally, I will show that the minimal frustration property can compel macroscopically simple behavior in otherwise complex, high-dimensional dynamical systems. This, in turn, has allowed us to develop useful network models of cell-fate choice without knowing all the underlying details. Towards the end, I will briefly describe how the minimal frustration framework may be extended beyond gene networks, to models of cell-cell interactions, to identify general features of population-level dynamics. Overall, I will present minimal frustration as a useful framework for analyzing the behavior of biological systems across contexts.
Hosts: Michael Abbott (michael.abbott@yale.edu), Isabella Graf (isabella.graf@yale.edu), and Mason Rouches (mason.rouches@yale.edu)
