Natural and synthetic mechanisms for emergent multicellular patterning : delayed signaling dynamics and bacterial self-assembly

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Abstract/Contents

Abstract
Natural multicellular organisms are capable of self-organizing intricate spatiotemporal patterns, often with single-cell precision. In contrast, our ability to understand and engineer multicellular spatial organization remains incredibly limited. In my thesis I approach this problem in two ways: (1) through a theoretical analysis of natural checkerboard patterns formed through lateral inhibition; and (2) by engineering the first 100% genetically encoded system for self-assembly of bacterial microstructures. For the first project, I noted that the delay in signal transduction between neighboring cells in lateral inhibition had not been explored. I developed a theoretical model including this delay explicitly, and found surprisingly that this delay precludes defects from forming within a differentiating tissue. In the second project, I noted that synthetic biologists have engineered a number of systems for differentiation and cell-cell signaling, but none for cell-cell adhesion. However, all three tools are crucial for multicellularity. I therefore developed a set of tunable, orthogonal, composable adhesins for cell-cell adhesion in Escherichia coli. The resulting tool enabled me to produce strains of bacteria that bind to one another to form cluster-, mesh-, and lattice-like arrangements, even while growing and dividing. Both projects help shed light on principles of self-organization. The adhesion system in particular will enable future development of synthetic multicellular systems for use in consortia-based metabolic engineering, in living materials, in tissue engineering, and in controlled study of minimal multicellular systems.

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 Glass, David Shaanan
Associated with Stanford University, Department of Bioengineering.
Primary advisor Riedel-Kruse, Hans
Thesis advisor Riedel-Kruse, Hans
Thesis advisor Endy, Andrew D
Thesis advisor Huang, Kerwyn Casey, 1979-
Thesis advisor Spormann, Alfred M
Advisor Endy, Andrew D
Advisor Huang, Kerwyn Casey, 1979-
Advisor Spormann, Alfred M

Subjects

Genre Theses

Bibliographic information

Statement of responsibility David Shaanan Glass.
Note Submitted to the Department of Bioengineering.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by David Shaanan Glass
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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