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Open Access Research

A modular positive feedback-based gene amplifier

Goutam J Nistala1, Kang Wu2, Christopher V Rao2* and Kaustubh D Bhalerao1

Author Affiliations

1 Department of Agricultural and Biological Engineering, University of Illinois at Urbana-Champaign, 1304 W Pennsylvania Ave, Urbana, IL, 61801, USA

2 Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S Mathews Ave, Urbana, IL, 61801, USA

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Journal of Biological Engineering 2010, 4:4  doi:10.1186/1754-1611-4-4

Published: 26 February 2010

Abstract

Background

Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors.

Results

We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity.

Conclusions

The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.