Toward a whole-cell model of Escherichia coli
Abstract/Contents
- Abstract
- Whole-cell computational models comprehensively simulate the growth and division of single cells, explicitly accounting for the functions of all known gene products and their interactions. Such models have the potential to revolutionize biology by serving as a platform to interpret complex behaviors, prioritize experiments, and enable design. In 2012, our lab completed the first whole-cell model of the simplest culturable organism, Mycoplasma genitalium. Since then we have focused our efforts on modeling Escherichia coli, one of the foundational model organisms in biology. In addition to having 10 times more genes and 50 times more molecules than M. genitalium, E. coli exhibits sophisticated regulation in response to environmental stimuli and perturbations. Currently, we have an E. coli model that incorporates the function of over 1200 genes and synthesizes tens of thousands of data points collected from both high- and low-throughput experiments performed over the last six decades. In building this model, we have incorporated many of E. coli's feedback control mechanisms, included hundreds of kinetic constraints in a model of metabolism, decreased simulation runtime more than ten-fold, and demonstrated the ability of our simulated cells to reliably reproduce over multiple generations. Furthermore, we have used the model to explore behaviors that arise from the interactions of multiple biological processes. In doing so, we have uncovered and quantified the prevalence of sub-generational gene expression. As the model continues to expand in size and scope, we hope that it will further our understanding of cell physiology and find practical applications in synthetic biology and medicine.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Macklin, Derek Nathaniel |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Covert, Markus |
| Thesis advisor | Covert, Markus |
| Thesis advisor | Altman, Russ |
| Thesis advisor | Bryant, Zev David |
| Advisor | Altman, Russ |
| Advisor | Bryant, Zev David |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Derek Nathaniel Macklin. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Derek Nathaniel Macklin
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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