A New Improved and Extended Version of the Multicell Bacterial Simulator gro

Abstract

gro is a cell programming language developed in Klavins Lab for simulating colony growth and cell-cell communication. It is used as a synthetic biology prototyping tool for simulating multicellular biocircuits and microbial consortia. In this work, we present several extensions made to gro that improve the performance of the simulator, make it easier to use, and provide new functionalities. The new version of gro is between 1 and 2 orders of magnitude faster than the original version. It is able to grow microbial colonies with up to 10 cells in less than 10 min. A new library, CellEngine, accelerates the resolution of spatial physical interactions between growing and dividing cells by implementing a new shoving algorithm. A genetic library, CellPro, based on Probabilistic Timed Automata, simulates gene expression dynamics using simplified and easy to compute digital proteins. We also propose a more convenient language specification layer, ProSpec, based on the idea that proteins drive cell behavior. CellNutrient, another library, implements Monod-based growth and nutrient uptake functionalities. The intercellular signaling management was improved and extended in a library called CellSignals. Finally, bacterial conjugation, another local cell-cell communication process, was added to the simulator. To show the versatility and potential outreach of this version of gro, we provide studies and novel examples ranging from synthetic biology to evolutionary microbiology. We believe that the upgrades implemented for gro have made it into a powerful and fast prototyping tool capable of simulating a large variety of systems and synthetic biology designs.

Spatial propagation of electrical signals in circular biofilms: A combined experimental and agent-based fire-diffuse-fire study

“…step of the simulation, diffusion and degradation are applied to update the concentrations of the signals over a set of predefined grids. Further details regarding the algorithms used in CELLENGINE, CELLPRO, and CELLSIGNAL can be found in Gutiérrez et al [27].…”

“…A range of different software packages have been developed to simulate cell colonies. We chose to build our ABM using the extended version of GRO [27] that functions well in two dimensions (2D), because it is a simple and fast simulator, which has been optimized for understanding the effects of colony spatial arrangement on cell-cell communication. The extended version of GRO relies on five major components:…”

From Microbial Communities to Distributed Computing Systems

“…Gro is a high-level framework for defining and simulating bacterial colony growth ( Jang et al, 2012 ). Gro has more recently been extended to include nutrient uptake and cell-cell signaling, enabling the simulation of spatial patterning in 2D ( Gutiérrez et al, 2017 ). Agent-based modeling frameworks DiSCUS and BactoSIM have been used to simulate conjugation processes in biofilms and how this effects the population as a whole ( García and Rodríguez-Patón, 2015 ; Goñi-Moreno and Amos, 2015 ); an important form of information propagation bacterial systems.…”

“…Here the space of two and three-node, stripe forming networks was investigated computationally, and used to inform wet laboratory experiments. Further computational investigation using the modeling platform GRO ( Jang et al, 2012 ; Gutiérrez et al, 2017 ) acts as a proof of concept for the design of bacterial colonies capable of self-assembling into spatial structures including L and T shapes ( Pascalie et al, 2016 ). It has also been shown that synthetic communities engineered to grow with a ring shaped pattern show scale invariance, similar to natural systems ( Cao et al, 2016 ).…”

Small Universal Bacteria and Plasmid Computing Systems

“…Using such conjugation, DNA molecules, acting as information carriers, can be transmitted from one cell to another. On the basis of the communication, information in one bacteria can be moved to another and can be used for further information processing [ 5 , 6 ].…”