A Synthetic Intercellular Toggle Switch and its Implications on Pattern Formation

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dc.contributor.advisorBennett, Matthew Ren_US
dc.creatorde Freitas Magalhaes, Barbaraen_US
dc.date.accessioned2021-12-06T20:03:19Zen_US
dc.date.created2021-12en_US
dc.date.issued2021-12-03en_US
dc.date.submittedDecember 2021en_US
dc.date.updated2021-12-06T20:03:20Zen_US
dc.description.abstractA genetic toggle switch is a circuit that possesses two stable mutually exclusive states of gene expression caused by cross-repression. It is widely found in natural processes, such as in development, given that cross-repression is important for refining pattern boundaries. Synthetically, many circuits that are applied to biotechnology are also based on toggle switches, such as many biosensors. However, single-cell synthetic genetic toggles are limited by individual noise fluctuations, and functions that do not cause metabolic load to the cell. Here, we propose the creation of an intercellular toggle switch, which is a synthetic toggle with quorum sensing (QS). QS is the mechanism through which bacteria communicate with each other, by producing signaling molecules that can affect gene expression in a density-dependent way. To overcome the main limitations of single-cell toggles, we aim to synchronize a population response, and enable circuit multicellularity through cell communication. Synthetic multicellular genetic circuits can perform complex functions that single cells cannot, and have the ability to better recreate naturally-occurring processes. In the first part, we describe the construction and characterization of a few QS toggle versions. We find that the dynamics of these toggle switches depend on their regulatory topologies, and their gene expression strength and leakiness. In the second part, we explore the aspects of one QS toggle version in a biofilm. We find that the QS toggle can form self-organized patterns when grown in a colony, by spatially segregating cells from different states. Comparatively, a non-QS (NQS) toggle colony does not show spatial-dependent pattern formation until three-dimensional aspects are investigated. NQS toggle shows a vertical segregation of states within colonies. It indicates that the addition of QS causes a directional shift in colony pattern behavior, and makes it more complex and dependent on growth, as shown with the mathematical model. These findings highlight the importance of spatial aspects to a synthetic circuit behavior. They also shed light into natural pattern formation mechanisms, and contribute to the development of synthetic self-organized multicellular systems in bacteria.en_US
dc.embargo.lift2023-12-01en_US
dc.embargo.terms2023-12-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationde Freitas Magalhaes, Barbara. "A Synthetic Intercellular Toggle Switch and its Implications on Pattern Formation." (2021) Diss., Rice University. <a href="https://hdl.handle.net/1911/111761">https://hdl.handle.net/1911/111761</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/111761en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjecttoggle switchen_US
dc.subjectquorum sensingen_US
dc.subjectspatial patternsen_US
dc.titleA Synthetic Intercellular Toggle Switch and its Implications on Pattern Formationen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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