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NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package

In 2008, we were among the first to propose a method for the visual design and modular modeling of synthetic gene circuits, mimicking the way electronic circuits are realized in silico. Basic components were DNA sequences that could be composed, first, into transcription units (TUs) and, then, circu...

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Autores principales: Abraha, Biruck Woldai, Marchisio, Mario Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961978/
https://www.ncbi.nlm.nih.gov/pubmed/35360404
http://dx.doi.org/10.3389/fbioe.2022.845240
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author Abraha, Biruck Woldai
Marchisio, Mario Andrea
author_facet Abraha, Biruck Woldai
Marchisio, Mario Andrea
author_sort Abraha, Biruck Woldai
collection PubMed
description In 2008, we were among the first to propose a method for the visual design and modular modeling of synthetic gene circuits, mimicking the way electronic circuits are realized in silico. Basic components were DNA sequences that could be composed, first, into transcription units (TUs) and, then, circuits by exchanging fluxes of molecules, such as PoPS (polymerase per second) and RiPS (ribosomes per seconds) as suggested by Drew Endy. However, it became clear soon that such fluxes were not measurable, which highlighted the limit of using some concepts from electronics to represent biological systems. SBML Level 3 with the comp package permitted us to revise circuit modularity, especially for the modeling of eukaryotic networks. By using the libSBML Python API, TUs—rather than single parts—are encoded in SBML Level 3 files that contain species, reactions, and ports, i.e., the interfaces that permit to wire TUs into circuits. A circuit model consists of a collection of SBML Level 3 files associated with the different TUs plus a “main” file that delineates the circuit structure. Within this framework, there is no more need for any flux of molecules. Here, we present the SBML Level 3-based models and the wet-lab implementations of Boolean NOT gates that make use, in the yeast Saccharomyces cerevisiae, of the bacterial ClpX-ClpP system for protein degradation. This work is the starting point towards a new piece of software for the modular design of eukaryotic gene circuits and shows an alternative way to build genetic Boolean gates.
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spelling pubmed-89619782022-03-30 NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package Abraha, Biruck Woldai Marchisio, Mario Andrea Front Bioeng Biotechnol Bioengineering and Biotechnology In 2008, we were among the first to propose a method for the visual design and modular modeling of synthetic gene circuits, mimicking the way electronic circuits are realized in silico. Basic components were DNA sequences that could be composed, first, into transcription units (TUs) and, then, circuits by exchanging fluxes of molecules, such as PoPS (polymerase per second) and RiPS (ribosomes per seconds) as suggested by Drew Endy. However, it became clear soon that such fluxes were not measurable, which highlighted the limit of using some concepts from electronics to represent biological systems. SBML Level 3 with the comp package permitted us to revise circuit modularity, especially for the modeling of eukaryotic networks. By using the libSBML Python API, TUs—rather than single parts—are encoded in SBML Level 3 files that contain species, reactions, and ports, i.e., the interfaces that permit to wire TUs into circuits. A circuit model consists of a collection of SBML Level 3 files associated with the different TUs plus a “main” file that delineates the circuit structure. Within this framework, there is no more need for any flux of molecules. Here, we present the SBML Level 3-based models and the wet-lab implementations of Boolean NOT gates that make use, in the yeast Saccharomyces cerevisiae, of the bacterial ClpX-ClpP system for protein degradation. This work is the starting point towards a new piece of software for the modular design of eukaryotic gene circuits and shows an alternative way to build genetic Boolean gates. Frontiers Media S.A. 2022-03-11 /pmc/articles/PMC8961978/ /pubmed/35360404 http://dx.doi.org/10.3389/fbioe.2022.845240 Text en Copyright © 2022 Abraha and Marchisio. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Abraha, Biruck Woldai
Marchisio, Mario Andrea
NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package
title NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package
title_full NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package
title_fullStr NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package
title_full_unstemmed NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package
title_short NOT Gates Based on Protein Degradation as a Case Study for a New Modular Modeling via SBML Level 3—Comp Package
title_sort not gates based on protein degradation as a case study for a new modular modeling via sbml level 3—comp package
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961978/
https://www.ncbi.nlm.nih.gov/pubmed/35360404
http://dx.doi.org/10.3389/fbioe.2022.845240
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