Library

eCommons

 

Characterization of RNA Genetic Regulators and Synthetic Networks

Simple item page
dc.contributor.authorWestbrook, Alexandra Michon
dc.contributor.chairLucks, Julius
dc.contributor.committeeMemberStroock, Abraham Duncan
dc.contributor.committeeMemberDaniel, Susan
dc.date.accessioned2018-10-23T13:33:13Z
dc.date.available2018-10-23T13:33:13Z
dc.date.issued2018-08-30
dc.description.abstractA central tenent of synthetic biology is the ability to predictably engineer complex patterns of gene expression. This fined tuned control allows us to reprogram organisms with sophisticated synthetic behaviors such as producing vital chemicals and drugs and sensing environmental signals. In order to do this we need libraries of highly efficient genetic regulators and proven methods of combining them into networks. RNA presents the ideal tool to build new genetic networks because its structural and temporal characteristics allow engineers to construct fast, designable genetic networks. In this work, we show characterization and optimization of new and existing RNA regulators as well as efforts to create new behaviors with RNA-based genetic networks. We begin by vastly improving the dynamic range of an existing transcriptional RNA regulator, the pT181 attenuator, by adding translational regulation. This dual control attenuator is successfully used to reduce circuit leak in an RNA-only cascade. In order to expand upon the functionality of the RNA repressors, we design sequesters that allow us to dial down repression. The sequestration effectively creates a threshold which we use to tune the relationship between the input and output of a system. As we construct more complex circuits with diverse parts, modularity becomes essential in order to predict circuit behavior. We explore the modularity of our RNA regulators in combination with clustered regularly interspaced short palindromic repeats (CRISPR) interference (CRISPRi) in construction of an RNA pulse generator. Finally, we explore the design and implementation two complex circuits: a communication network for delivering complex signals to cells and a control network to reduce noise in biological systems. We anticipate that the design rules learned and the tools developed here will allow construction of even more sophisticated behaviors as the growing discipline of genetic design matures.
dc.identifier.doihttps://doi.org/10.7298/X4SB4401
dc.identifier.otherWestbrook_cornellgrad_0058F_11067
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:11067
dc.identifier.otherbibid: 10489637
dc.identifier.urihttps://hdl.handle.net/1813/59541
dc.language.isoen_US
dc.subjectRNA
dc.subjectBiological control
dc.subjectBioengineering
dc.subjectBiological Networks
dc.subjectsynthetic biology
dc.titleCharacterization of RNA Genetic Regulators and Synthetic Networks
dc.typedissertation or thesis
dcterms.licensehttps://hdl.handle.net/1813/59810
thesis.degree.disciplineChemical Engineering
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Chemical Engineering

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Westbrook_cornellgrad_0058F_11067.pdf
Size:
8.89 MB
Format:
Adobe Portable Document Format
Download

Collections

Cornell Theses and Dissertations