File Download
Supplementary

postgraduate thesis: Self-organizing pattern formation of synthetic multicellular systems

TitleSelf-organizing pattern formation of synthetic multicellular systems
Authors
Advisors
Advisor(s):Fung, MLHuang, J
Issue Date2018
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Zhou, N. [周楠]. (2018). Self-organizing pattern formation of synthetic multicellular systems. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.
AbstractAmazing biological structures and patterns are generated by multicellular organisms. Self-organization is a hallmark of the pattern formation process. Patterns typically arise from coordinated cellular behaviors, such as the spatial arrangement of specialized cell types to generate tissues and to form complex body layouts. Such coordination, commonly orchestrated at the population level, can be achieved by mutual interactions among different cell species. The overwhelming complexity of living systems, however, makes deciphering the underlying mechanisms difficult and limits our knowledge of basic pattern-forming mechanisms in vivo. A successful strategy is then to work with synthetic, engineered systems, in which cellular interactions are programmed with well-studied processes. In this study, a simple mechanism was demonstrated to enable two different populations of E. coli cells to self-organize into periodic stripe patterns controlled by synthetic genetic circuits. The synthetic genetic circuits were constructed by wiring a bidirectional and orthogonal intercellular signaling mediated through Lux and Las quorum sensing systems, which send out a quorum sensing signal from each of the cell population. The two distinct intercellular signals reciprocally activate the expression of a motility effector gene, cheZ, in the other cell population. Thus, the two strains were programmed to control the cellular motility of each other in a density-dependent manner. When mixed and spotted on a semi solid agar plate, the two populations of E. coli cells spontaneously organized into alternating, out-of-phase concentric rings, without the need of any preexisting positional or orientational cues. By re-designing the interaction, a variant synthetic multicellular system, in which the motility of each strain was negatively correlated with the density of their conjugate species, was subsequently constructed. In contrast to the original out-of-phase spatial oscillation rhythm, the two engineered populations were turned into in-phase oscillations with the mutual repression system. The density-dependent motility control was further illustrated as a generic self-organization mechanism to direct autonomous aggregation or segregation between different cell species. This was achieved by engineering a third sensor strain whose motility was exclusively controlled by the density of the other species. The generic mechanism was demonstrated to be able to induce self-organized spatial structures of more complex synthetic multicellular systems involving over two cellular species. The robustness and versatility of this interspecies motility interaction-based pattern formation mechanism suggest its utilization by natural biological systems.
DegreeDoctor of Philosophy
SubjectSynthetic biology
Dept/ProgramBiomedical Sciences
Persistent Identifierhttp://hdl.handle.net/10722/271621

 

DC FieldValueLanguage
dc.contributor.advisorFung, ML-
dc.contributor.advisorHuang, J-
dc.contributor.authorZhou, Nan-
dc.contributor.author周楠-
dc.date.accessioned2019-07-10T03:19:02Z-
dc.date.available2019-07-10T03:19:02Z-
dc.date.issued2018-
dc.identifier.citationZhou, N. [周楠]. (2018). Self-organizing pattern formation of synthetic multicellular systems. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.-
dc.identifier.urihttp://hdl.handle.net/10722/271621-
dc.description.abstractAmazing biological structures and patterns are generated by multicellular organisms. Self-organization is a hallmark of the pattern formation process. Patterns typically arise from coordinated cellular behaviors, such as the spatial arrangement of specialized cell types to generate tissues and to form complex body layouts. Such coordination, commonly orchestrated at the population level, can be achieved by mutual interactions among different cell species. The overwhelming complexity of living systems, however, makes deciphering the underlying mechanisms difficult and limits our knowledge of basic pattern-forming mechanisms in vivo. A successful strategy is then to work with synthetic, engineered systems, in which cellular interactions are programmed with well-studied processes. In this study, a simple mechanism was demonstrated to enable two different populations of E. coli cells to self-organize into periodic stripe patterns controlled by synthetic genetic circuits. The synthetic genetic circuits were constructed by wiring a bidirectional and orthogonal intercellular signaling mediated through Lux and Las quorum sensing systems, which send out a quorum sensing signal from each of the cell population. The two distinct intercellular signals reciprocally activate the expression of a motility effector gene, cheZ, in the other cell population. Thus, the two strains were programmed to control the cellular motility of each other in a density-dependent manner. When mixed and spotted on a semi solid agar plate, the two populations of E. coli cells spontaneously organized into alternating, out-of-phase concentric rings, without the need of any preexisting positional or orientational cues. By re-designing the interaction, a variant synthetic multicellular system, in which the motility of each strain was negatively correlated with the density of their conjugate species, was subsequently constructed. In contrast to the original out-of-phase spatial oscillation rhythm, the two engineered populations were turned into in-phase oscillations with the mutual repression system. The density-dependent motility control was further illustrated as a generic self-organization mechanism to direct autonomous aggregation or segregation between different cell species. This was achieved by engineering a third sensor strain whose motility was exclusively controlled by the density of the other species. The generic mechanism was demonstrated to be able to induce self-organized spatial structures of more complex synthetic multicellular systems involving over two cellular species. The robustness and versatility of this interspecies motility interaction-based pattern formation mechanism suggest its utilization by natural biological systems.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject.lcshSynthetic biology-
dc.titleSelf-organizing pattern formation of synthetic multicellular systems-
dc.typePG_Thesis-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineBiomedical Sciences-
dc.description.naturepublished_or_final_version-
dc.date.hkucongregation2018-
dc.identifier.mmsid991044058185103414-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats