Modularity and predictability in cell signaling and decision making.
Bottom Line: Even within a genetically identical population of cells grown in the same environment, cell-to-cell variations in mRNA and protein concentrations can be as high as 50% in yeast and even higher in mammalian cells.Here we discuss the implications of recent advances in genomics, single-cell, and single-cell genomics technology for network modularity and cellular decisions.On the basis of these recent advances, we argue that most gene expression stochasticity and pathway interconnectivity is nonfunctional and that cellular decisions are likely much more predictable than previously expected.
Affiliation: Department of Biology, Stanford University, Stanford, CA 94305.Show MeSH
Related in: MedlinePlus
Mentions: Moreover, it is likely that there are additional hierarchies of organization from network to pathway to even smaller groups of signaling molecules known as motifs (Figure 1). This hierarchical organization is in part due to the separate time scales of biological interactions. For instance, phosphorylation reactions are very fast, whereas protein synthesis and corresponding concentration changes are relatively slow. This allows analysis of phosphorylation kinetics of a few pathway components comprising a motif while treating protein concentrations as fixed. Thus the motif's dynamics can be studied in depth, and its function can be characterized. Indeed, motif analysis has made great progress in determining signaling principles (Alon, 2007), suggesting a view of biology as tractable, modular on several scales, and, it is hoped, ultimately predictable. According to this view, with sufficient understanding of networks and signaling principles, we should be able to understand how cells process information and predict what the output of a cellular decision will be from the measurements of regulatory proteins.
Affiliation: Department of Biology, Stanford University, Stanford, CA 94305.