Pulse Detecting Genetic Circuit - A New Design Approach.

A robust cellular counter could enable synthetic biologists to design complex circuits with diverse behaviors. The existing synthetic-biological counters, responsive to the beginning of the pulse, are sensitive to the pulse duration. Here we present a pulse detecting circuit that responds only at th...

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Main Authors: Nasimul Noman, Mara Inniss, Hitoshi Iba, Jeffrey C Way
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5131961?pdf=render
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author Nasimul Noman
Mara Inniss
Hitoshi Iba
Jeffrey C Way
author_facet Nasimul Noman
Mara Inniss
Hitoshi Iba
Jeffrey C Way
author_sort Nasimul Noman
collection DOAJ
description A robust cellular counter could enable synthetic biologists to design complex circuits with diverse behaviors. The existing synthetic-biological counters, responsive to the beginning of the pulse, are sensitive to the pulse duration. Here we present a pulse detecting circuit that responds only at the falling edge of a pulse-analogous to negative edge triggered electric circuits. As biological events do not follow precise timing, use of such a pulse detector would enable the design of robust asynchronous counters which can count the completion of events. This transcription-based pulse detecting circuit depends on the interaction of two co-expressed lambdoid phage-derived proteins: the first is unstable and inhibits the regulatory activity of the second, stable protein. At the end of the pulse the unstable inhibitor protein disappears from the cell and the second protein triggers the recording of the event completion. Using stochastic simulation we showed that the proposed design can detect the completion of the pulse irrespective to the pulse duration. In our simulation we also showed that fusing the pulse detector with a phage lambda memory element we can construct a counter which can be extended to count larger numbers. The proposed design principle is a new control mechanism for synthetic biology which can be integrated in different circuits for identifying the completion of an event.
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spelling doaj.art-1f279ca59f934f84a0d3528b1d02eec02022-12-22T00:40:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011112e016716210.1371/journal.pone.0167162Pulse Detecting Genetic Circuit - A New Design Approach.Nasimul NomanMara InnissHitoshi IbaJeffrey C WayA robust cellular counter could enable synthetic biologists to design complex circuits with diverse behaviors. The existing synthetic-biological counters, responsive to the beginning of the pulse, are sensitive to the pulse duration. Here we present a pulse detecting circuit that responds only at the falling edge of a pulse-analogous to negative edge triggered electric circuits. As biological events do not follow precise timing, use of such a pulse detector would enable the design of robust asynchronous counters which can count the completion of events. This transcription-based pulse detecting circuit depends on the interaction of two co-expressed lambdoid phage-derived proteins: the first is unstable and inhibits the regulatory activity of the second, stable protein. At the end of the pulse the unstable inhibitor protein disappears from the cell and the second protein triggers the recording of the event completion. Using stochastic simulation we showed that the proposed design can detect the completion of the pulse irrespective to the pulse duration. In our simulation we also showed that fusing the pulse detector with a phage lambda memory element we can construct a counter which can be extended to count larger numbers. The proposed design principle is a new control mechanism for synthetic biology which can be integrated in different circuits for identifying the completion of an event.http://europepmc.org/articles/PMC5131961?pdf=render
spellingShingle Nasimul Noman
Mara Inniss
Hitoshi Iba
Jeffrey C Way
Pulse Detecting Genetic Circuit - A New Design Approach.
PLoS ONE
title Pulse Detecting Genetic Circuit - A New Design Approach.
title_full Pulse Detecting Genetic Circuit - A New Design Approach.
title_fullStr Pulse Detecting Genetic Circuit - A New Design Approach.
title_full_unstemmed Pulse Detecting Genetic Circuit - A New Design Approach.
title_short Pulse Detecting Genetic Circuit - A New Design Approach.
title_sort pulse detecting genetic circuit a new design approach
url http://europepmc.org/articles/PMC5131961?pdf=render
work_keys_str_mv AT nasimulnoman pulsedetectinggeneticcircuitanewdesignapproach
AT marainniss pulsedetectinggeneticcircuitanewdesignapproach
AT hitoshiiba pulsedetectinggeneticcircuitanewdesignapproach
AT jeffreycway pulsedetectinggeneticcircuitanewdesignapproach