how to turn a genetic circuit into a synthetic tunable oscillator, or a bistable switch如何将一个基因电路合成可调振荡器,还是双稳态开关.pdfVIP

How to Turn a Genetic Circuit into a Synthetic Tunable Oscillator, or a Bistable Switch 1,2 3 4 1 1 Lucia Marucci , David A. W. Barton , Irene Cantone , Maria Aurelia Ricci , Maria Pia Cosma , Stefania Santini2, Diego di Bernardo1,2.*, Mario di Bernardo2,3.* 1Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy, 2 Department of Computer and Systems Engineering, Federico II University, Naples, Italy, 3 Bristol Centre for Applied Nonlinear Mathematics, University of Bristol, Bristol, United Kingdom, 4 MRC Clinical Sciences Centre Faculty of Medicine, Imperial College London, London, United Kingdom Abstract Systems and Synthetic Biology use computational models of biological pathways in order to study in silico the behaviour of biological pathways. Mathematical models allow to verify biological hypotheses and to predict new possible dynamical behaviours. Here we use the tools of non-linear analysis to understand how to change the dynamics of the genes composing a novel synthetic network recently constructed in the yeast Saccharomyces cerevisiae for In-vivo Reverse- engineering and Modelling Assessment (IRMA). Guided by previous theoretical results that make the dynamics of a biological network depend on its topological properties, through the use of simulation and continuation techniques, we found that the network can be easily turned into a robust and tunable synthetic oscillator or a bistable switch. Our results provide guidelines to properly re-engineering in vivo the network in order to tune its dynamics. Citation: Marucci L, Barton DAW, Cantone I, Ricci MA, Cosma MP, et al. (2009) How to Turn a Genetic Circuit into a Synthetic Tunable Oscill