The E. coli Whole-Cell Modeling Project

Sun, Gwanggyu; Ahn-Horst, Travis A.; Covert, Markus W.

doi:10.1128/ecosalplus.esp-0001-2020

Cited by 18 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the process, it also helps to explain mechanistically how growth rate control operates in responding to changing conditions. We anticipate that this new functionality, and the insights it can catalyze, will support a variety of new applications with and expansions of the E. coli Whole-Cell Modeling Project 17 .…”

Section: Discussionmentioning

confidence: 97%

“…This highly integrative method can therefore bridge both mechanistic and empirical approaches, and in the process can provide a deep understanding of changes that happen throughout the entire cell. Whole-cell modeling was first conceived in the 1970s by Francis Crick 10 , followed by Michael Shuler 11 Harold Morowitz 12 and Masaru Tomita 13 , but it was first demonstrated decades later in M. genitalium , the smallest culturable organism 14 , 15 , and has more recently been applied to E. coli 16 , 17 . Using whole-cell models to capture behavior of single cells allows for integration and assessment of heterogeneous datasets and the scientific community’s current understanding of biological interactions through mechanistic relationships.…”

Section: Introductionmentioning

confidence: 99%

“…Using whole-cell models to capture behavior of single cells allows for integration and assessment of heterogeneous datasets and the scientific community’s current understanding of biological interactions through mechanistic relationships. Although the original E. coli whole-cell model described in Macklin et al 16 accounted for many of the processes and physiology of E. coli , including the central dogma, metabolism and regulation, the E. coli Whole-Cell Modeling Project 17 is an ongoing effort to expand the scope of the E. coli whole-cell model by including missing gene and small molecule functionality as well as increasing the number of possible nutrient conditions for simulated growth.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An expanded whole-cell model of E. coli links cellular physiology with mechanisms of growth rate control

et al. 2022

Self Cite

View full text Add to dashboard Cite

Growth and environmental responses are essential for living organisms to survive and adapt to constantly changing environments. In order to simulate new conditions and capture dynamic responses to environmental shifts in a developing whole-cell model of E. coli, we incorporated additional regulation, including dynamics of the global regulator guanosine tetraphosphate (ppGpp), along with dynamics of amino acid biosynthesis and translation. With the model, we show that under perturbed ppGpp conditions, small molecule feedback inhibition pathways, in addition to regulation of expression, play a role in ppGpp regulation of growth. We also found that simulations with dysregulated amino acid synthesis pathways provide average amino acid concentration predictions that are comparable to experimental results but on the single-cell level, concentrations unexpectedly show regular fluctuations. Additionally, during both an upshift and downshift in nutrient availability, the simulated cell responds similarly with a transient increase in the mRNA:rRNA ratio. This additional simulation functionality should support a variety of new applications and expansions of the E. coli Whole-Cell Modeling Project.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An expanded whole-cell model of E. coli links cellular physiology with mechanisms of growth rate control

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…This focus on simulation rather than understanding may explain why, after a series of improvements, the project, while still existing (https://www.e-cell.org/about.html) progressively stalled. At present, the whole‐cell modelling of E. coli follows another turn, still based on standard approaches but with some input of stochasticity to take into account entities that are present at a low number in cells (Sun et al ., 2021).…”

Section: Synthetic Biology In Silicomentioning

confidence: 99%

In vivo, in vitro and in silico: an open space for the development of microbe‐based applications of synthetic biology

Danchin

2021

Microbial Biotechnology

View full text Add to dashboard Cite

Living systems are studied using three complementary approaches: living cells, cell-free systems and computer-mediated modelling. Progresses in understanding, allowing researchers to create novel chassis and industrial processes rest on a cycle that combines in vivo, in vitro and in silico studies. This design-build-test-learn iteration loop cycle between experiments and analyses combines together physiology, genetics, biochemistry and bioinformatics in a way that keeps going forward. Because computeraided approaches are not directly constrained by the material nature of the entities of interest, we illustrate here how this virtuous cycle allows researchers to explore chemistry which is foreign to that present in extant life, from whole chassis to novel metabolic cycles. Particular emphasis is placed on the importance of evolution.

show abstract

“…Further advances of synthetic biology tools such as standardized DNA assembly and innovative genome manipulation tools allow the quick establishment of new microbial systems. In addition to this, many high-throughput technologies are broadly available for in-depth characterization, such as transcriptome, proteome and metabolome profiling allowing researchers to accumulate large-scale datasets with the potential to create whole-cell models (Sun et al, 2021;Lu et al, 2022). This is due to the efforts of interdisciplinary work between experimentalists, data scientists and software engineers to constantly improve software tools, many of which are now able to be used in a plug-and-play manner by any user.…”

Section: Introductionmentioning

confidence: 99%

Microbes of traditional fermentation processes as synthetic biology chassis to tackle future food challenges

Rojas

Swidah

Schindler

2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Microbial diversity is magnificent and essential to almost all life on Earth. Microbes are an essential part of every human, allowing us to utilize otherwise inaccessible resources. It is no surprise that humans started, initially unconsciously, domesticating microbes for food production: one may call this microbial domestication 1.0. Sourdough bread is just one of the miracles performed by microbial fermentation, allowing extraction of more nutrients from flour and at the same time creating a fluffy and delicious loaf. There are a broad range of products the production of which requires fermentation such as chocolate, cheese, coffee and vinegar. Eventually, with the rise of microscopy, humans became aware of microbial life. Today our knowledge and technological advances allow us to genetically engineer microbes - one may call this microbial domestication 2.0. Synthetic biology and microbial chassis adaptation allow us to tackle current and future food challenges. One of the most apparent challenges is the limited space on Earth available for agriculture and its major tolls on the environment through use of pesticides and the replacement of ecosystems with monocultures. Further challenges include transport and packaging, exacerbated by the 24/7 on-demand mentality of many customers. Synthetic biology already tackles multiple food challenges and will be able to tackle many future food challenges. In this perspective article, we highlight recent microbial synthetic biology research to address future food challenges. We further give a perspective on how synthetic biology tools may teach old microbes new tricks, and what standardized microbial domestication could look like.

show abstract

The E. coli Whole-Cell Modeling Project

Abstract: The Escherichia coli whole-cell modeling project seeks to create the most detailed computational model of an E. coli cell in order to better understand and predict the behavior of this model organism. Details about the approach, framework, and current version of the model are discussed.

Cited by 18 publications

References 45 publications

An expanded whole-cell model of E. coli links cellular physiology with mechanisms of growth rate control

An expanded whole-cell model of E. coli links cellular physiology with mechanisms of growth rate control

In vivo, in vitro and in silico: an open space for the development of microbe‐based applications of synthetic biology

Microbes of traditional fermentation processes as synthetic biology chassis to tackle future food challenges

Contact Info

Product

Resources

About