A genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice

Author:

Greiss FerdinandORCID,Lardon Nicolas,Schütz Leonie,Barak Yoav,Daube Shirley S.ORCID,Weinhold Elmar,Noireaux VincentORCID,Bar-Ziv RoyORCID

Abstract

AbstractRealizing genetic circuits on single DNA molecules as self-encoded dissipative nanodevices is a major step toward miniaturization of autonomous biological systems. A circuit operating on a single DNA implies that genetically encoded proteins localize during coupled transcription-translation to DNA, but a single-molecule measurement demonstrating this has remained a challenge. Here, we use a genetically encoded fluorescent reporter system with improved temporal resolution and observe the synthesis of individual proteins tethered to a DNA molecule by transient complexes of RNA polymerase, messenger RNA, and ribosome. Against expectations in dilute cell-free conditions where equilibrium considerations favor dispersion, these nascent proteins linger long enough to regulate cascaded reactions on the same DNA. We rationally design a pulsatile genetic circuit by encoding an activator and repressor in feedback on the same DNA molecule. Driven by the local synthesis of only several proteins per hour and gene, the circuit dynamics exhibit enhanced variability between individual DNA molecules, and fluctuations with a broad power spectrum. Our results demonstrate that co-expressional localization, as a nonequilibrium process, facilitates single-DNA genetic circuits as dissipative nanodevices, with implications for nanobiotechnology applications and artificial cell design.

Funder

Israel Science Foundation

United States - Israel Binational Science Foundation

Minerva Foundation

Isak Ferdinand and Dwosia Artmann Research Fund for Biological Physics

European Molecular Biology Organization

German-Israeli Foundation for Scientific Research and Development

United States-Israel Binational Science Foundation

Human Frontier Science Program

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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