title: A formalized design process for bacterial consortia that perform logic computing.
abstract: The concept of microbial consortia is of great attractiveness in synthetic biology. Despite of all its benefits, however, there are still problems remaining for large-scaled multicellular gene circuits, for example, how to reliably design and distribute the circuits in microbial consortia with limited number of well-behaved genetic modules and wiring quorum-sensing molecules. To manage such problem, here we propose a formalized design process: (i) determine the basic logic units (AND, OR and NOT gates) based on mathematical and biological considerations; (ii) establish rules to search and distribute simplest logic design; (iii) assemble assigned basic logic units in each logic operating cell; and (iv) fine-tune the circuiting interface between logic operators. We in silico analyzed gene circuits with inputs ranging from two to four, comparing our method with the pre-existing ones. Results showed that this formalized design process is more feasible concerning numbers of cells required. Furthermore, as a proof of principle, an Escherichia coli consortium that performs XOR function, a typical complex computing operation, was designed. The construction and characterization of logic operators is independent of "wiring" and provides predictive information for fine-tuning. This formalized design process provides guidance for the design of microbial consortia that perform distributed biological computation.
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Ji
authors.forename: Handuo
authors.initials: H
authors.lastname: Shi
authors.forename: Haoqian
authors.initials: H
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Jingyi
authors.initials: J
authors.lastname: Xi
authors.forename: Dingqiao
authors.initials: D
authors.lastname: Wen
authors.forename: Jingchen
authors.initials: J
authors.lastname: Feng
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Qin
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Ma
authors.forename: Wenhan
authors.initials: W
authors.lastname: Luo
authors.forename: Linna
authors.initials: L
authors.lastname: Deng
authors.forename: Hanchi
authors.initials: H
authors.lastname: Lin
authors.forename: Ruofan
authors.initials: R
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D058615:Synthetic Biology