title: Synthetic analog computation in living cells.
abstract: A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.
authors.affiliation: Analog Circuits and Biological Systems Group, Research Lab of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Ramiz
authors.initials: R
authors.lastname: Daniel
authors.forename: Jacob R
authors.initials: JR
authors.lastname: Rubens
authors.forename: Rahul
authors.initials: R
authors.lastname: Sarpeshkar
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Lu
mesh_terms: D015374:Biosensing Techniques / Q000379:methods; D001709:Biotechnology / Q000379:methods; D003198:Computer Simulation; D003202:Computers, Analog; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D008128:Logic; D050296:Microbial Viability; D008954:Models, Biological; D053038:Quorum Sensing; D058615:Synthetic Biology / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors