Synthetic analog computation in living cells

Synthetic analog gene circuits can be engineered to execute logarithmically linear sensing, addition, ratiometric and power-law computations in living cells using just three transcription factors. Living-cell computation simplified The design of novel genetic control systems for synthetic biology is dominated by digital logic. This is necessarily a complex arrangement. Now Timothy Lu and colleagues have harnessed analog building-blocks found in natural cells to perform arithmetic operations in the logarithmic domain. Such analog circuits — which could be integrated with digital — should make it possible to use fewer components to implement complex computations that require wide dynamic range in biosensing. A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications 1 . 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 2 , 3 . 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 4 , 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 3 , 5 , 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.