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Timing molecular motion and production with a synthetic transcriptional clock

Franco, Elisa and Friedrichs, Eike and Kim, Jongmin and Jungmann, Ralf and Murray, Richard M. and Winfree, Erik and Simmel, Friedrich C. (2011) Timing molecular motion and production with a synthetic transcriptional clock. Proceedings of the National Academy of Sciences of the United States of America, 108 (40). E784-E793 . ISSN 0027-8424. PMCID PMC3189071.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription DOIArticle CentralArticle
Franco, Elisa0000-0003-1103-2668
Murray, Richard M.0000-0002-5785-7481
Winfree, Erik0000-0002-5899-7523
Additional Information:© 2011 by the National Academy of Sciences. Freely available online through the PNAS open access option. Edited by David Baker, University of Washington, Seattle, WA, and approved August 9, 2011 (received for review January 17, 2011). We are especially grateful to Eric Klavins for coining the irresistible moniker “genelets,” to Maximilian Weitz for control measurements, and to Franco Blanchini for mathematical advice. The authors acknowledge financial support by the Human Frontier Science Program (HFSP) grant no. RGY 74/2006, the European Commission FP7 grant no. 248919 (BACTOCOM), the National Science Foundation (NSF) grants nos. NIRT-0608889 and CCF-0832824 (The Molecular Programming Project), the Institute for Collaborative Biotechnologies (grant DAAD19-03-D-0004 from the Army Research Office), and the Nanosystems Initiative Munich (NIM). Author contributions: E. Franco, E. Friedrichs, J.K., E.W., and F.C.S. designed research; E. Franco and E. Friedrichs performed research; E. Franco, E. Friedrichs, J.K., R.J., R.M., E.W., and F.C.S. analyzed data; and E. Franco, E. Friedrichs, J.K., R.J., E.W., and F.C.S. wrote the paper.
Funding AgencyGrant Number
Human Frontier Science ProgramRGY 74/2006
European Commission248919 (BACTOCOM)
Army Research Office (ARO) DAAD19-03-D-0004
Nanosystems Initiative MunichUNSPECIFIED
Subject Keywords:cell-free circuits; modularity; genelets; DNA nanotechnology
Issue or Number:40
PubMed Central ID:PMC3189071
Record Number:CaltechAUTHORS:20111020-091851903
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:27324
Deposited By: Tony Diaz
Deposited On:24 Oct 2011 22:20
Last Modified:02 Jun 2020 20:48

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