An incoherent feed‐forward loop (FFL) is one of the most‐frequently observed motifs in biomolecular regulatory networks. It has been thought that the incoherent FFL is designed simply to induce a transient response shaped by a ‘fast activation and delayed inhibition’. We find that the dynamics of various incoherent FFLs can be further classified into two types: time‐dependent biphasic responses and dose‐dependent biphasic responses. Why do the structurally identical incoherent FFLs play such different dynamical roles? Through computational studies, we show that (...) the dynamics of the two types of incoherent FFLs are mutually exclusive. Following from further computational results and experimental observations, we hypothesize that incoherent FFLs have been optimally designed to achieve distinct biological function arising from different cellular contexts. Additional Supporting Information may be found in the online version of the article. BioEssays 30:1204–1211, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The identification of network motifs has been widely considered as a significant step towards uncovering the design principles of biomolecular regulatory networks. To date, time‐invariant networks have been considered. However, such approaches cannot be used to reveal time‐specific biological traits due to the dynamic nature of biological systems, and hence may not be applicable to development, where temporal regulation of gene expression is an indispensable characteristic. We propose a concept of a “temporal sequence of network motifs”, a sequence of network (...) motifs in active sub‐networks constructed over time, and investigate significant network motifs in the active temporal sub‐networks of Drosophila melanogaster. Based on this concept, we find a temporal sequence of network motifs which changes according to developmental stages and thereby cannot be identified from the whole static network. Moreover, we show that the temporal sequence of network motifs corresponding to each developmental stage can be used to describe pivotal developmental events. (shrink)

Cellular circuits have positive and negative feedback loops that allow them to respond properly to noisy external stimuli. It is intriguing that such feedback loops exist in many cases in a particular form of coupled positive and negative feedback loops with different time delays. As a result of our mathematical simulations and investigations into various experimental evidences, we found that such coupled feedback circuits can rapidly turn on a reaction to a proper stimulus, robustly maintain its status, and immediately turn (...) off the reaction when the stimulus disappears. In other words, coupled feedback loops enable cellular systems to produce perfect responses to noisy stimuli with respect to signal duration and amplitude. This suggests that coupled positive and negative feedback loops form essential signal transduction motifs in cellular signaling systems. BioEssays 29: 85–90, 2007. © 2006 Wiley Periodicals, Inc. (shrink)

Cover Photograph: Resolving developmental genetics in the fourth dimension: an illustration (by Kwang‐Hyun Cho himself) of the principle of dynamic network motifs in Drosophila development. Hitherto largely considered in terms of time‐invariant networks, drosophila development is viewed in the article by Man‐Sun Kim, Jeong‐Rae Kim, and Kwang‐Hyun Cho as the result of networks of gene interactions that change during the course of development. Using this paradigm, pivotal developmental events can be correlated with particular changes from one constellation of gene interactions (...) to a different one, and the method allows the identification of certain network motifs that are not identifiable using static approaches. Features article: “Dynamic network rewiring determines temporal regulatory functions in the Drosophila melanogaster development processes”, see pages 505 – 513. (shrink)