scholarly journals Computational Re-design of Synthetic Genetic Oscillators for Independent Amplitude and Frequency Modulation

Cell Systems ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 508-520.e5 ◽  
Author(s):  
Marios Tomazou ◽  
Mauricio Barahona ◽  
Karen M. Polizzi ◽  
Guy-Bart Stan
2017 ◽  
Author(s):  
M. Tomazou ◽  
M. Barahona ◽  
K. Polizzi ◽  
G.-B. Stan

AbstractEngineering robust and tuneable genetic clocks is a topic of current interest in Systems and Synthetic Biology with wide applications in biotechnology. Synthetic genetic oscillators share a common structure based on a negative feedback loop with a time delay, and generally display only limited tuneability. Recently, the dual-feedback oscillator was demonstrated to be robust and tuneable, to some extent, by the use of chemical inducers. Yet no engineered genetic oscillator currently allows for the independent modulation of amplitude and period. In this work, we demonstrate computationally how recent advances in tuneable synthetic degradation can be used to decouple the frequency and amplitude modulation in synthetic genetic oscillators. We show how the range of tuneability can be increased by connecting additional input dials, e.g. orthogonal transcription factors that respond to chemical, temperature or even light signals. Modelling and numerical simulations predict that our proposed re-designs enable amplitude tuning without period modulation, coupled modulation of both period and amplitude, or period adjustment with near-constant amplitude. We illustrate our work through computational re-designs of both the dual-feedback oscillator and the repressilator, and show that the repressilator is more flexible and can allow for independent amplitude and near-independent period modulation.


1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S171 ◽  
Author(s):  
H. HARMS ◽  
U. KAPTAINA ◽  
T. KÜLPMANN ◽  
R.-D. HESCH

2005 ◽  
Vol 26 (3) ◽  
pp. 409-422 ◽  
Author(s):  
L Bellomonte ◽  
I Guastella ◽  
R M Sperandeo-Mineo

2012 ◽  
Vol 1422 ◽  
Author(s):  
Santiago D. Solares ◽  
Gaurav Chawla

ABSTRACTMulti-frequency atomic force microscopy (AFM) offers additional response signals in comparison to traditional dynamic AFM. Furthermore, depending on the mode of operation used, the higher eigenmode responses are generally not directly influenced by the topographical acquisition control loops, such that they can explore a fuller range of tip-sample interactions. In this work we describe the implementation of multi-frequency imaging schemes that enable the acquisition of topographical, phase and frequency shift contrast in tapping-mode operation. This type of characterization can be especially useful for soft, highly dissipative samples, such as polymers, for which the various response channels can exhibit significantly different response, thus providing complementary information. We discuss typical results obtained as well as important challenges that need to be addressed in order to develop a fully quantitative technique.


2018 ◽  
Vol 104 (5) ◽  
pp. 778-782 ◽  
Author(s):  
Brian C. J. Moore ◽  
Sashi Mariathasan ◽  
Aleksander P. Se¸k

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