Multistability and predominant hybrid phenotypes in a four node mutually repressive network of Th1/Th2/Th17/Treg differentiation.

Elucidating the emergent dynamics of cellular differentiation networks is crucial to understanding cell-fate decisions. Toggle switch - a network of mutually repressive lineage-specific transcription factors A and B - enables two phenotypes from a common progenitor: (high A, low B) and (low A, high B). However, the dynamics of networks enabling differentiation of more than two phenotypes from a progenitor cell has not been well-studied.

Quantifying robustness of the gap gene network.

Early development of Drosophila melanogaster (fruit fly) facilitated by the gap gene network has been shown to be incredibly robust, and the same patterns emerge even when the process is seriously disrupted. We investigate this robustness using a previously developed computational framework called DSGRN (Dynamic Signatures Generated by Regulatory Networks). Our mathematical innovations include the conceptual extension of this established modeling technique to enable modeling of spatially monotone environmental effects, as well as the development of a collection of graph theoretic robustness scores for network models.