Computational simulations of whole cells : strategies for framework design and model parameterization

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Abstract/Contents

Abstract
The complexity of living systems, and the mounting wealth of biological data, poses a challenge: can we unify our comprehension of a living system into one coherent representation - and if so, what would we learn? Herein I present strategies for the design of a framework that can integrate diverse mathematical submodels of cellular physiology into one hybrid computational simulation of a whole cell, extending and revising prior work in this space. This framework is realized in the form of a whole-cell model of E. coli that can dynamically reproduce several molecular, cellular, and population-level behaviors across multiple environments and cell cycles. I also present strategies for integrative parameter estimation in the context of whole-cell-like submodels, an emergent need consequent of limited or inconsistent biological data. This work identifies model formulation and parameterization techniques that facilitate exploration of the space of biological dynamics; it also identifies specific inconsistencies in the underlying data as well as systems-level hypotheses about metabolic control and dynamics. Altogether, this research comprises several conceptual and technical advancements towards the end of functionally complete single-cell simulations.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2018; ©2018
Publication date 2018; 2018
Issuance monographic
Language English

Creators/Contributors

Author Mason, John Christopher
Degree supervisor Covert, Markus
Thesis advisor Covert, Markus
Thesis advisor Altman, Russ
Thesis advisor Huang, Kerwyn Casey, 1979-
Degree committee member Altman, Russ
Degree committee member Huang, Kerwyn Casey, 1979-
Associated with Stanford University, Department of Bioengineering.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility John Mason.
Note Submitted to the Department of Bioengineering.
Thesis Thesis Ph.D. Stanford University 2018.
Location electronic resource

Access conditions

Copyright
© 2018 by John Christopher Mason
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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