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Modeling a Minimal Cell

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Microbial Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 881))

Abstract

One important aim of synthetic biology is to develop a self-replicating biological system capable of performing useful tasks. A mathematical model of a synthetic organism would greatly enhance its value by providing a platform in which proposed modifications to the system could be rapidly prototyped and tested. Such a platform would allow the explicit connection of genomic sequence information to physiological predictions. As an initial step toward this aim, a minimal cell model (MCM) has been formulated. The MCM is defined as a model of a hypothetical cell with the minimum number of genes necessary to grow and divide in an optimally supportive culture environment. It is chemically detailed in terms of genes and gene products, as well as physiologically complete in terms of bacterial cell processes (e.g., DNA replication and cell division). A mathematical framework originally developed for modeling Escherichia coli has been used to build the platform MCM. A MCM with 241 product-coding genes (those which produce protein or stable RNA products) is presented. This gene set is genomically complete in that it codes for all the functions that a minimal chemoheterotrophic bacterium would require for sustained growth and division. With this model, the hypotheses behind a minimal gene set can be tested using a chemically detailed, dynamic, whole-cell modeling approach. Furthermore, the MCM can simulate the behavior of a whole cell that depends on the cell’s (1) metabolic rates and chemical state, (2) genome in terms of expression of various genes, (3) environment both in terms of direct nutrient starvation and competitive inhibition leading to starvation, and (4) genomic sequence in terms of the chromosomal locations of genes.

Portions of this chapter are reused, with permission, from J. C. Atlas, “Simulation of a Whole-Cell With the Minimum Number of Genes Necessary for Sustained Replication.” PhD thesis, Cornell University, 2010.

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Acknowledgements

JA gratefully acknowledges funding from the DOE Computational Science Graduate Fellowship Program (CSGF) of the Office of Science and National Nuclear Security Administration in the DOE under contract DE-FG02-97ER25308.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA

    Michael L. Shuler & Jordan Atlas

  2. School of Chemical Engineering, Cornell University, Ithaca, NY, USA

    Patricia Foley

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  1. Michael L. Shuler
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  2. Patricia Foley
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  3. Jordan Atlas
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Correspondence to Michael L. Shuler .

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  1. Physics & Life Sciences Directorate, Biosciences & Biotechnology Div., Lawrence Livermore National Laboratory, East Avenue 7000, Livermore, 94551, California, USA

    Ali Navid

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Shuler, M.L., Foley, P., Atlas, J. (2012). Modeling a Minimal Cell. In: Navid, A. (eds) Microbial Systems Biology. Methods in Molecular Biology, vol 881. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-827-6_20

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  • DOI: https://doi.org/10.1007/978-1-61779-827-6_20

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