Abstract
Synthetic biologists engineer cells and cellular functions using design-build-test cycles; when the task is to extensively engineer entire genomes, the lack of appropriate design tools and biological knowledge about each gene in a cell can lengthen the process, requiring time-consuming and expensive experimental iterations.Whole-cell models represent a new avenue for genome design; the bacteria Mycoplasma genitalium has the first (and currently only published) whole-cell model which combines 28 cellular submodels and represents the integrated functions of every gene and molecule in a cell.We created two minimal genome design algorithms, GAMA and Minesweeper, that produced 1000s of in silico minimal genomes by running simulations on multiple supercomputers. Here we describe the steps to produce in silico cells with reduced genomes, combining minimisation algorithms with whole-cell model simulations.We foresee that the combination of similar algorithms and whole-cell models could later be used for a broad spectrum of genome design applications across cellular species when appropriate models become available.
Original language | English |
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Pages (from-to) | 183-198 |
Number of pages | 16 |
Journal | Methods in Molecular Biology |
Volume | 2189 |
DOIs | |
Publication status | Published - 13 Nov 2020 |
Bibliographical note
Funding Information:LM is supported by the Medical Research Council grant MR/N021444/1, by the Engineering and Physical Sciences Research Council grants EP/R041695/1 and EP/S01876X/1, and by the European Union?s Horizon 2020 under Grant Agreement No. 766840. OC, LM and CG are supported by a BrisSyn-Bio, a BBSRC/EPSRC Synthetic Biology Research Centre (BB/L01386X/1), flexi-fund grant. OC is supported by the Bristol Centre for Complexity Sciences (BCCS) Centre for Doctoral Training (CDT) EP/I013717/1. JR-G is supported by an EPSRC Future Opportunity scholarship.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Research Groups and Themes
- Bristol BioDesign Institute
Keywords
- Computer Simulation
- synthetic biology
- Mycoplasma genitalium/genetics
- Algorithms
- Genetic Engineering
- Synthetic Biology
- Genome, Bacterial
- Models, Genetic
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Dive into the research topics of 'Minimal Genome Design Algorithms Using Whole-Cell Models'. Together they form a unique fingerprint.Student theses
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Minimal Genome Design and Engineering: Algorithms and whole-cell Models
Rees-Garbutt, J. P. (Author), Marucci, L. (Supervisor) & Grierson, C. (Supervisor), 26 Nov 2020Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)
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Datasets
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Data from minimal gene set whole-cell modelling
Marucci, L. (Creator), Grierson, C. (Creator), Chalkley, O. (Creator), Rees, J. (Creator) & Rightmyer, J. (Creator), University of Bristol, 30 Apr 2021
DOI: 10.5523/bris.356boayld729v2snyncfoltt0w, http://data.bris.ac.uk/data/dataset/356boayld729v2snyncfoltt0w
Dataset
Equipment
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HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility