Synthetic Gene Networks that Count

By Ari E. Friedland, Timothy K. Lu, Xiao Wang, David Shi, George M. Church, James J. Collins. Science, 2009

596 citations recorded by the source corpus.

One, Two, Three Synthetic biologists take much of their inspiration from computing and electrical engineering, attempting to gain programmability in cells using analogous genetic circuits. Friedland et al. (p. 1199; see the Perspective by Smolke) have constructed complementary Escherichia coli synthetic gene networks that keep track of prior molecular events to function as counters. These modular devices count up to three induction events over a range of frequencies and could be extended to higher numbers. Similar devices may find application in multi-event processes of cell biology, bioengineering, and, potentially, therapeutics. Genetic counters with the ability to count up to three induction events are constructed in Escherichia coli. Synthetic gene networks can be constructed to emulate digital circuits and devices, giving one the ability to program and design cells with some of the principles of modern computing, such as counting. A cellular counter would enable complex synthetic programming and a variety of biotechnology applications. Here, we report two complementary synthetic genetic counters in Escherichia coli that can count up to three induction events: the first, a riboregulated transcriptional cascade, and the second, a recombinase-based cascade of memory units. These modular devices permit counting of varied user-defined inputs over a range of frequencies and can be expanded to count higher numbers.

Subfields: Biophysics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dc334e9d238accea2c29d95324b08fd4c6333d21

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Citations in the corpus

The Emerging Paradigm of Network Medicine in the Study of Human Disease (2012, methodology): “6 “Sensitivity analysis,” or so-called “metabolic control analysis” (MCA), is used to compute sensitivity coefficients, which generally reflect the ratios between the change in the biochemical network behavior (as monitored by some measure of global system behavior) and the perturbation on specific…”
Automated Design of Synthetic Ribosome Binding Sites to Precisely Control Protein Expression (2009, methodology): “Using the transfer functions, fitness function and equation (3), we created (3) Figure 4 Optimal connection of a sensor input to an AND gate genetic circuit.”
Basis for a neuronal version of Grover's quantum algorithm (2014, unknown): “…cell biology toward trends in logic gate, circuit, and algorithm designs (e.g., Ehrenfeucht et al., 2003; Amos, 2006; Baumgardner et al., 2009; Friedland et al., 2009; Adamatzky, 2010; Clark, 2010a,b,c,d, 2011, 2012b, 2013a; Norris et al., 2011; Karafyllidis, 2012; Mehta and Schwab, 2012;…”
Biomolecular computing systems: principles, progress and potential (2012, background): “This was overcome in another study that used a set of invertases to count the number of chemical pulses in yeast cells 121 .”
Toehold Switches: De-Novo-Designed Regulators of Gene Expression (2014, unknown): “Synthetic gene networks have been used to construct a wide range of biological devices, including molecular counters (Friedland et al., 2009), oscillators (Elowitz and Leibler, 2000), toggle switches (Gardner et al., 2000), logic gates (Ausländer et al., 2012; Moon et al., 2012; Siuti et al.,…”
A synchronized quorum of genetic clocks (2010, unknown): “…23 have inspired the design and construction of circuits capable of controlling cellular population growth 24 , generating specific patterns 25 , triggering biofilm development 26 , shaping intracellular noise 27 , detecting edges in an image 28 , and counting discrete cellular events 29 .”