Title :
Synthetic Biology: A Unifying View and Review Using Analog Circuits
Author :
Teo, Jonathan J. Y. ; Sung Sik Woo ; Sarpeshkar, Rahul
Author_Institution :
Res. Lab. of Electron., Massachusetts Inst. of Technol., Cambridge, MA, USA
Abstract :
We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic´ approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.
Keywords :
Boltzmann equation; DNA; RNA; analogue circuits; biochemistry; biomolecular electronics; cellular biophysics; molecular biophysics; partial differential equations; proteins; reviews; Boltzmann thermodynamic equations; DNA; RNA; analog computation; analog electronic circuit design; biochemical reactions; canonical analog circuit; cytomorphic approach; digital circuit operation; dynamic ordinary differential equations; feedback analog circuits; feedforward analog circuits; living cells; molecular circuits; noisy electronic current flow; noisy molecular flux; nonlinear differential equations; partial differential equations; protein; review; saturated analog circuit behavior; small-molecule levels; stochastic noisy ordinary differential equations; subthreshold transistors; synthetic biology; Analog circuits; Generators; Logic gates; Noise; Proteins; Synthetic biology; Transistors; Analog circuits; biological circuit design; cellular engineering; cytomorphic; feedback; resource consumption; review; synthetic biology analog computation;
Journal_Title :
Biomedical Circuits and Systems, IEEE Transactions on
DOI :
10.1109/TBCAS.2015.2461446