Prof. Sui Huang (Institute for Systems Biology, Seattle)

Abstract

The idea that genotype maps directly and deterministically into the phenotype has dictated evolution biology as well as cancer biology where cancer progression is understood as driven by a somatic Darwinian evolution of cells that accumulate mutations and undergo selection. In reality, one genome can produce thousands of stable and inherited phenotypes, most prosaically manifest in the many natural cell types of the metazoan body – which sit in the valleys in Waddington’s epigenetic landscape. Waddington’s landscape metaphor explains phenotypic variability (“plasticity”) in the absence of genetic alterations and can be grounded in the mathematical principles of gene regulatory network dynamics.  Herein, a given stable cell type is a high-dimensional attractor state. But then, how do cells switch phenotypes, as in development, if cell types are so robust? We proposed that cell fate decisions and ensuing state transitions are bifurcation events in which attractor states are destabilized, manifest as…