Implementation of complex biological logic circuits using spatially distributed multicellular consortia

Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit's complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined.This work was supported by an ERC Advanced Grant Number 294294 from the EU seventh framework program (SYNCOM) to RS and FP, and the Santa Fe Institute to RS. FP and RS laboratories are also supported by Fundación Botín, by Banco Santander through its Santander Universities Global Division. The laboratory of FP and EdN is supported by grants from the Spanish Government (BFU2012-33503/ BFU2015-64437 P and FEDER to FP; BFU2014-52333-P and FEDER to EdN) and the Catalan Government (2014 SGR 599). The research leading to these results has received funding from “la Caixa” Foundation in collaboration with “Centre per a la Innovació de la Diabetis Infantil Sant Joan de Déu (CIDI)”. FP and EdN are recipients of an ICREA Acadèmia (Generalitat de Catalunya). RM was a former EMBO postdoctoral fellow. AU is a recipient of a “La Caixa” fellowship