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Simple molecular networks that respond optimally to time-periodic stimulation

DOI: 10.1186/1752-0509-3-29

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Abstract:

We took a look at basic network motifs studied in the literature such as the Incoherent Feedforward Loop (IFFL) or the interlerlocked negative feedback loop. The former is also generalized to a diamond pattern, with network components being either purely genetic or combining genetic and signaling pathways. Using standard mathematics and numerical simulations, we explain the types of responses exhibited by the IFFL with respect to a train of periodic pulses. We show that this system has a non-vanishing response only if the inter-pulse interval is above a threshold. A slight generalisation of the IFFL (the diamond) is shown to work as an ideal pass-band filter. We next show a mechanism by which average of oscillatory response can be maximized by bursting temporal patterns. Finally we study the interlerlocked negative feedback loop, i.e. a 2-gene motif forming a loop where the nodes respectively activate and repress each other, and show situations where this system possesses a resonance under periodic stimulation.We present several simple motif designs of molecular networks producing optimal output in response to periodic stimulations of the system. The identified mechanisms are simple and based on known network motifs in the literature, so that that they could be embodied in existing organisms, or easily implementable by means of synthetic biology. Moreover we show that these designs can be studied in different contexts of molecular biology, as for example in genetic networks or in signaling pathways.For past several decades, the experimental data concerning protein concentrations in biological regulatory networks have mostly been obtained in conditions related to stationary states. In some natural contexts, however, or in some experiments, the relevant cellular response to measure is the one the cell displays when it is exposed to time-dependent signals. Such information can be essential to unravelling the regulatory principles of those molecular networks which by na

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