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A multi-functional synthetic gene network: a frequency multiplier, oscillator and switch.

Purcell O, di Bernardo M, Grierson CS, Savery NJ - PLoS ONE (2011)

Bottom Line: Analysis of the bifurcation structure also reveals novel, programmable multi-functionality; in addition to functioning as a frequency multiplier, the network is able to function as a switch or an oscillator, depending on the temporal nature of the input.Multi-functionality is often observed in neuronal networks, where it is suggested to allow for the efficient coordination of different responses.This network represents a significant theoretical addition that extends the capabilities of synthetic gene networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Mathematics, Bristol Centre for Complexity Sciences, University of Bristol, Bristol, United Kingdom. enoep@bristol.ac.uk

ABSTRACT
We present the design and analysis of a synthetic gene network that performs frequency multiplication. It takes oscillatory transcription factor concentrations, such as those produced from the currently available genetic oscillators, as an input, and produces oscillations with half the input frequency as an output. Analysis of the bifurcation structure also reveals novel, programmable multi-functionality; in addition to functioning as a frequency multiplier, the network is able to function as a switch or an oscillator, depending on the temporal nature of the input. Multi-functionality is often observed in neuronal networks, where it is suggested to allow for the efficient coordination of different responses. This network represents a significant theoretical addition that extends the capabilities of synthetic gene networks.

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Related in: MedlinePlus

Frequency multiplication for a sine input with an offset.Time series for the repressors R1–R4 and the input are shown in the top and bottom panels respectively. The concentrations of R1, R2, R3 and R4 are represented by pink, black, orange and green lines respectively. Initial conditions:  nM,  nM. The input is the following function: , where , p is the period, t is time, a is amplitude and  is the minimum of the input.  nM. Parameters from table 1 are used.
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pone-0016140-g004: Frequency multiplication for a sine input with an offset.Time series for the repressors R1–R4 and the input are shown in the top and bottom panels respectively. The concentrations of R1, R2, R3 and R4 are represented by pink, black, orange and green lines respectively. Initial conditions: nM, nM. The input is the following function: , where , p is the period, t is time, a is amplitude and is the minimum of the input. nM. Parameters from table 1 are used.

Mentions: However, in order to integrate with existing genetic oscillators in vivo the network must be capable of performing frequency multiplication on a continuously oscillating input. Numerical simulations showed the network performing frequency multiplication of one half on an oscillating input with a period of 90000 seconds (25 hours) (see File S3). We confirmed that frequency multiplication was also possible with a slightly weaker repressor of M (data not shown) (the parameters used are given in File S2). Furthermore, the oscillators constructed so far in vivo do not generally reach a zero level in between oscillations [14]. A frequency multiplier must therefore be capable of working with oscillations that have a non-zero minimum, or offset. Figure 4 demonstrates the network performing frequency multiplication on an oscillating input with an input minimum of 6 nM. This is approximately 10% of the maximum level, comparable to oscillations generated by the recently constructed robust oscillator in [11].


A multi-functional synthetic gene network: a frequency multiplier, oscillator and switch.

Purcell O, di Bernardo M, Grierson CS, Savery NJ - PLoS ONE (2011)

Frequency multiplication for a sine input with an offset.Time series for the repressors R1–R4 and the input are shown in the top and bottom panels respectively. The concentrations of R1, R2, R3 and R4 are represented by pink, black, orange and green lines respectively. Initial conditions:  nM,  nM. The input is the following function: , where , p is the period, t is time, a is amplitude and  is the minimum of the input.  nM. Parameters from table 1 are used.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040778&req=5

pone-0016140-g004: Frequency multiplication for a sine input with an offset.Time series for the repressors R1–R4 and the input are shown in the top and bottom panels respectively. The concentrations of R1, R2, R3 and R4 are represented by pink, black, orange and green lines respectively. Initial conditions: nM, nM. The input is the following function: , where , p is the period, t is time, a is amplitude and is the minimum of the input. nM. Parameters from table 1 are used.
Mentions: However, in order to integrate with existing genetic oscillators in vivo the network must be capable of performing frequency multiplication on a continuously oscillating input. Numerical simulations showed the network performing frequency multiplication of one half on an oscillating input with a period of 90000 seconds (25 hours) (see File S3). We confirmed that frequency multiplication was also possible with a slightly weaker repressor of M (data not shown) (the parameters used are given in File S2). Furthermore, the oscillators constructed so far in vivo do not generally reach a zero level in between oscillations [14]. A frequency multiplier must therefore be capable of working with oscillations that have a non-zero minimum, or offset. Figure 4 demonstrates the network performing frequency multiplication on an oscillating input with an input minimum of 6 nM. This is approximately 10% of the maximum level, comparable to oscillations generated by the recently constructed robust oscillator in [11].

Bottom Line: Analysis of the bifurcation structure also reveals novel, programmable multi-functionality; in addition to functioning as a frequency multiplier, the network is able to function as a switch or an oscillator, depending on the temporal nature of the input.Multi-functionality is often observed in neuronal networks, where it is suggested to allow for the efficient coordination of different responses.This network represents a significant theoretical addition that extends the capabilities of synthetic gene networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Mathematics, Bristol Centre for Complexity Sciences, University of Bristol, Bristol, United Kingdom. enoep@bristol.ac.uk

ABSTRACT
We present the design and analysis of a synthetic gene network that performs frequency multiplication. It takes oscillatory transcription factor concentrations, such as those produced from the currently available genetic oscillators, as an input, and produces oscillations with half the input frequency as an output. Analysis of the bifurcation structure also reveals novel, programmable multi-functionality; in addition to functioning as a frequency multiplier, the network is able to function as a switch or an oscillator, depending on the temporal nature of the input. Multi-functionality is often observed in neuronal networks, where it is suggested to allow for the efficient coordination of different responses. This network represents a significant theoretical addition that extends the capabilities of synthetic gene networks.

Show MeSH
Related in: MedlinePlus