Researchers Synchronize Blinking 'Genetic Clocks' -- Genetically Engineered Bacteria That Keep Track of Time
ScienceDaily (Jan. 24, 2010) — Researchers at UC San Diego who last year genetically engineered bacteria to keep track of time by turning on and off fluorescent proteins within their cells have taken another step toward the construction of a programmable genetic sensor. The scientists recently synchronized these bacterial "genetic clocks" to blink in unison and engineered the bacterial genes to alter their blinking rates when environmental conditions change.
A supernova burst in a colony of coupled genetic clocks show them flashing in synchrony. (Credit: UCSD)
"Programming living cells is one defining goal of the new field of synthetic biology," said Jeff Hasty, associate professor of biology and bioengineering at UCSD who headed the research team with Lev Tsimring, associate director of UCSD's BioCircuits Institute.
"Dr. Hasty and colleagues have used powerful genetic tools, backed by decades of detailed knowledge of bacterial processes, to create a system that delivers on the promise of synthetic biology -- to engineer living organisms to meet pressing societal needs," said James Anderson, who oversees computational biology grants at the NIH's National Institute of General Medical Sciences. "The oscillating system they engineered sets the stage for the development of highly sensitive sensors that could have multiple applications in basic research, biotechnology and medicine."
"Synchronization of clocks and oscillators in general has been a fascinating subject for physicists and applied mathematicians for centuries," said Tsimring. "This began with the Dutch mathematician and astronomer Christiaan Huygens, who is credited with its serendipitous discovery in 1665 when he suspended a pair of nearly identical pendulum clocks (which he invented and patented some 8 years earlier) on the same wooden beam."
"Synchronization plays a crucial role in physics and biology as a way of self-organization of highly regular behavior with less that perfect components. This phenomenon has a myriad of applications in modern technology, from communication networks to GPS. Our study demonstrates how inherently noisy gene oscillators can operate together with beautiful synchronicity and regularity once coupled together in a specific way."
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ArticleNature 463, 326-330 (21 January 2010) | doi:10.1038/nature08753; Received 20 August 2009; Accepted 4 December 2009
Tal Danino1,4, Octavio Mondragón-Palomino1,4, Lev Tsimring2 & Jeff Hasty1,2,3
Department of Bioengineering,
BioCircuits Institute, University of California, San Diego, La Jolla, California 92093, USA
Molecular Biology Section, Division of Biological Science, University of California, Mailcode 0368, La Jolla, California 92093, USA
These authors contributed equally to this work.
Correspondence to: Jeff Hasty1,2,3 Correspondence and requests for materials should be addressed to J.H. (Email: hasty@bioeng.ucsd.edu).
Abstract
The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic biology. This focus was elegantly set in motion a decade ago with the design and construction of a genetic toggle switch and an oscillator, with subsequent highlights that have included circuits capable of pattern generation, noise shaping, edge detection and event counting. Here we describe an engineered gene network with global intercellular coupling that is capable of generating synchronized oscillations in a growing population of cells. Using microfluidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring at millimetre scales. We use computational modelling to describe quantitatively the observed dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock sets the stage for the use of microbes in the creation of a macroscopic biosensor with an oscillatory output. Furthermore, it provides a specific model system for the generation of a mechanistic description of emergent coordinated behaviour at the colony level.
Department of Bioengineering,
BioCircuits Institute, University of California, San Diego, La Jolla, California 92093, USA
Molecular Biology Section, Division of Biological Science, University of California, Mailcode 0368, La Jolla, California 92093, USA
These authors contributed equally to this work.
Correspondence to: Jeff Hasty1,2,3 Correspondence and requests for materials should be addressed to J.H. (Email: hasty@bioeng.ucsd.edu).
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