title: Distributed biological computation with multicellular engineered networks.
abstract: Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices using engineered biological units as basic building blocks. Such efforts, inspired in the standard design of electronic circuits, are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations.
authors.affiliation: Cell signaling unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), E-08003 Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Regot
authors.forename: Javier
authors.initials: J
authors.lastname: Macia
authors.forename: Núria
authors.initials: N
authors.lastname: Conde
authors.forename: Kentaro
authors.initials: K
authors.lastname: Furukawa
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kjellén
authors.forename: Tom
authors.initials: T
authors.lastname: Peeters
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohmann
authors.forename: Eulàlia
authors.initials: E
authors.lastname: de Nadal
authors.forename: Francesc
authors.initials: F
authors.lastname: Posas
authors.forename: Ricard
authors.initials: R
authors.lastname: Solé
mesh_terms: D057005:Bioengineering; D002176:Candida albicans; D002451:Cell Compartmentation; D015169:Colony Count, Microbial; D004318:Doxycycline / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D008128:Logic; D000072235:Mating Factor; D008954:Models, Biological; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010675:Pheromones / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D049490:Systems Biology / Q000379:methods*
chemical_list: D010455:Peptides; D010675:Pheromones; D012965:Sodium Chloride; D004958:Estradiol; D000072235:Mating Factor; D004318:Doxycycline; D005690:Galactose