A synthetic mammalian electro-genetic transcription circuit

Abstract

Electric signal processing has evolved to manage rapid information transfer in neuronal networks and muscular contraction in multicellular organisms and controls the most sophisticated man-built devices. Using a synthetic biology approach to assemble electronic parts with genetic control units engineered into mammalian cells, we designed an electric power-adjustable transcription control circuit able to integrate the intensity of a direct current over time, to translate the amplitude or frequency of an alternating current into an adjustable genetic readout or to modulate the beating frequency of primary heart cells. Successful miniaturization of the electro-genetic devices may pave the way for the design of novel hybrid electro-genetic implants assembled from electronic and genetic parts.

A Brief Introduction to Synthetic Biology

“…Fussenegger et al, have even created a transgene design, incorporated into mammalian circuits leading to synthetic networks that are responsive to electrical signals. (Weber et al 2009). …”

Synthetic Biology and Microdevices

“…A synthetic electrogenic device using electricity-induced expression of specific transgenes is recently developed in mammalian cells [Weber et al 2008]. This device allows creating an interface managing mutual exchange of information between mammalian cells and electronic processing units (see Figure 5).…”

“…This electrical input signal triggers the production of human placental SEAP, which can be subsequently detected by an enzymatic-optical process consisting of a photodiode that produces a dose-dependent electrical signal. (Figure adapted from [Weber et al 2008]) 4.6 Optical stimulation of micro-organisms regulated by an in silico closed-loop control system…”

“…Microengineered platforms not only allow maintaining and feeding micro-organisms by providing fluidics and reagents through microchannels, but also allow controlling and monitoring the cellular behavior by signal detection and analysis which can give rise to new analytical approaches for the characterization of biological parts [Weibel et al 2007;Bennett and Hasty 2009;Gulati et al 2009;van der Meer and Belkin 2010;Vinuselvi et al 2011]. Since the scale of microelectronics matches well the physical dimensions of micro-organisms, the processing capabilities of micro-organisms can be further exploited by integrating whole-cell elements into microelectronics Weber et al 2008]. This review will rather give a biological view on how the combination of microbiology with microfluidics and microelectronics can give rise to new analytical technologies and novel bioelectronic devices, and emphasizes the need to bring biologists, physicists and engineers together in order to enhance and fully exploit the multidisciplinarity of synthetic biology.…”

Recent advances in mammalian synthetic biology—design of synthetic transgene control networks

“…Owing to their importance and success in basic and applied research a panoply of such heterologous transcription control modalities have been developed that are responsive to all kinds of small molecules. Since most mammalian transcription control systems have a generic circuit topology and a common genetic design they are functionally compatible and therefore seen by synthetic biologists as biological parts that could be assembled to higher order genetic control devices and regulatory networks that are approaching the complexity of electronic circuits [8,9,10 ]. Such synthetic networks reveal novel control dynamics [11] or provide prosthetic circuits for future therapeutic applications.…”