title: Pulse Detecting Genetic Circuit - A New Design Approach.
abstract: 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.
authors.affiliation: School of Electrical Engineering and Computer Science, The University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Nasimul
authors.identifier: http://orcid.org/0000-0002-8566-0870
authors.initials: N
authors.lastname: Noman
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Mara
authors.initials: M
authors.lastname: Inniss
authors.affiliation: Department of Information and Communication Engineering, Graduate School of Information Science and Technology, The University of Tokyo, Bunkyo, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iba
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA, United States of America.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Way
mesh_terms: D010582:Bacteriophage lambda / Q000502:physiology; D015374:Biosensing Techniques; D015870:Gene Expression; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D008957:Models, Genetic; D058615:Synthetic Biology / Q000379:methods*