Timing molecular motion and production with a synthetic transcriptional clock

The realization of artificial biochemical reaction networks with unique functionality is one of the main challenges for the development of synthetic biology. Due to the reduced number of components, biochemical circuits constructed in vitro promise to be more amenable to systematic design and quanti...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2011-10, Vol.108 (40), p.E784-E793
Main Authors: Franco, Elisa, Friedrichs, Eike, Kim, Jongmin, Jungmann, Ralf, Murray, Richard, Winfree, Erik, Simmel, Friedrich C
Format: Article
Language:English
Subjects:
Aptamers, Nucleotide - genetics
Aptamers, Nucleotide - metabolism
Biological Clocks - physiology
Biological Sciences
Chemical reactions
Deoxyribonucleic acid
DNA
insulating materials
Insulation
malachite green
Models, Biological
Molecules
Nanostructures
Nanotechnology
oligonucleotides
Physical Sciences
PNAS Plus
Ribonucleic acid
RNA
Rosaniline Dyes - metabolism
synthetic biology
Synthetic Biology - methods
transcription (genetics)
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Summary:The realization of artificial biochemical reaction networks with unique functionality is one of the main challenges for the development of synthetic biology. Due to the reduced number of components, biochemical circuits constructed in vitro promise to be more amenable to systematic design and quantitative assessment than circuits embedded within living organisms. To make good on that promise, effective methods for composing subsystems into larger systems are needed. Here we used an artificial biochemical oscillator based on in vitro transcription and RNA degradation reactions to drive a variety of "load" processes such as the operation of a DNA-based nanomechanical device ("DNA tweezers") or the production of a functional RNA molecule (an aptamer for malachite green). We implemented several mechanisms for coupling the load processes to the oscillator circuit and compared them based on how much the load affected the frequency and amplitude of the core oscillator, and how much of the load was effectively driven. Based on heuristic insights and computational modeling, an "insulator circuit" was developed, which strongly reduced the detrimental influence of the load on the oscillator circuit. Understanding how to design effective insulation between biochemical subsystems will be critical for the synthesis of larger and more complex systems.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1100060108