Biocircuit design through engineering bacterial logic gates

Goñi-Moreno, Ángel; Redondo‐Nieto, Miguel; Arroyo, Fernando; Castellanos, Juan

doi:10.1007/s11047-010-9184-2

Cited by 26 publications

(16 citation statements)

References 23 publications

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“…An important recent development in synthetic biology and biocomputing has been the development of computational consortia; that is, computations that are distributed over a number of different cells, each of which performs a specific role [29,30,31]. This approach potentially allows for much more scalable cellular computation, as a large and potentially complex circuit may be broken down into smaller communicating components, each of which is placed in a specific cell.…”

Section: Resultsmentioning

confidence: 99%

Dynamical Task Switching in Cellular Computers

Goñi-Moreno

Cruz

Rodríguez‐Patón

et al. 2019

Life

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Section: Resultsmentioning

confidence: 99%

Dynamical Task Switching in Cellular Computers

Goñi-Moreno

Cruz

Rodríguez‐Patón

et al. 2019

Life

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“…Relatively simple models of computation, like combinatorial [7] and sequential logic [8], have been successfully implemented in organisms such as bacteria [9], yeasts [10] or even mammalian cells [11]. Examples of these genetic circuits include logic gates [12,13], multiplexers [14], half-adders [15], counters [16] and memories [17]-even more complex processes such as analogue [18,19] and distributed computations [20,21,22]. As well as generating fundamental insights into the workings of living systems, this (and many more) engineered systems find a broad range of applications in biotechnology and bioengineering [23,24].…”

Section: Introductionmentioning

confidence: 99%

Modelling co-translational dimerisation for programmable nonlinearity in synthetic biology

Stoof

Goñi-Moreno

2020

Preprint

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Nonlinearity plays a fundamental role in the performance of both natural and synthetic biological networks. Key functional motifs in living microbial systems, such as the emergence of bistability or oscillations, rely on nonlinear molecular dynamics. Despite its core importance, the rational design of nonlinearity remains an unmet challenge. This is largely due to a lack of mathematical modelling that accounts for the mechanistic basics of nonlinearity. We introduce a model for gene regulatory circuits that explicitly simulates protein dimerization—a well-known source of nonlinear dynamics. Specifically, our approach focusses on modelling co-translational dimerization: the formation of protein dimers during—and not after—translation. This is in contrast to the prevailing assumption that dimer generation is only viable between freely diffusing monomers (i.e., post-translational dimerization). We provide a method for fine-tuning nonlinearity on demand by balancing the impact of co- versus post-translational dimerization. Furthermore, we suggest design rules, such as protein length or physical separation between genes, that may be used to adjust dimerization dynamics in-vivo. The design, build and test of genetic circuits with on-demand nonlinear dynamics will greatly improve the programmability of synthetic biological systems.

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“…Central to the implementation of multicellular computation is controlled communication between cells and populations of cells. So far, this has generally been implemented using the global communication capabilities offered by quorum sensing (QS) [13]–[15] (although the use of bacteriophage has also recently been proposed [16]). Within the QS system, one cell (sender) uses small signalling molecules that diffuse over distance and thus reach other cells (receivers) [17].…”

Section: Introductionmentioning

confidence: 99%

Multicellular Computing Using Conjugation for Wiring

2013

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Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal “re-programming” and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a “computation” is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the “wiring” between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing system under different conditions, and provide baseline information for future laboratory implementations.

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Biocircuit design through engineering bacterial logic gates

Cited by 26 publications

References 23 publications

Dynamical Task Switching in Cellular Computers

Dynamical Task Switching in Cellular Computers

Modelling co-translational dimerisation for programmable nonlinearity in synthetic biology

Multicellular Computing Using Conjugation for Wiring

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