%0 Journal Article
%T A modular positive feedback-based gene amplifier
%A Goutam J Nistala
%A Kang Wu
%A Christopher V Rao
%A Kaustubh D Bhalerao
%J Journal of Biological Engineering
%D 2010
%I BioMed Central
%R 10.1186/1754-1611-4-4
%X 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.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.Positive feedback is a common mechanism involved in the regulation of genetic circuits [1]. Any time a gene product has the capacity to enhance its own production, either directly or indirectly, the circuit is said to involve positive feedback. A number of behaviors can be attributed to positive feedback loops. The defining one is clearly amplification. More complex behaviors include bistability and hysteresis. In addition, positive feedback is an integral element in many oscillatory, pattern-formation, and intracellular polarization processes [2,3].In a number of synthetic biology applications, positive feedback has been used to design switches, oscillators, and amplifiers. Besckei and coworkers [4], for example, showed in yeast that a simple positive feedback loop could transform a graded response to an inducer into a binary one. Likewise, Kramer and Fussenegger [5] showed that positive feedback could be u
%U http://www.jbioleng.org/content/4/1/4