Speaker
Description
Biological systems are thought to be hierarchically modular, such that small semi-autonomous modules work together to create larger modules, each responsible for function at a different scale of organization. We thus expect that understanding each module in isolation and putting them together tells us how the whole works. When it comes to cellular regulation, however, a registry of biological modules and their behaviors do not appear to be not sufficient to decipher their coordinated response. Here we ask: are there are general rules by which cellular functions are coordinated in health and disease? We hypothesize that distinct phenotype-combinations are generated by interactions among several multistable regulatory switches, each in control of a discrete set of phenotypic outcomes. To test whether this organization sets apart regulatory networks from random ones, we define measures that quantify whether a) a Boolean network's dynamics can be accurately described via combinations of module-autonomous dynamics, b) modules preserve dynamical autonomy while coupled to others, and c) switches at all scales of the hierarchy show robustness in their phenotype-choice control. Comparing a modular mammalian cell cycle model to its randomized counterparts, we formulate three general principles that govern the way coupled switches coordinate their function. These principles can guide construction of large Boolean regulatory models that reproduce a broad range of observed cell behaviors.
