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Mitigating the effects of ribosome limitations on synthetic circuits via high-gain sRNA-mediated negative feedback

Thesis: S.M., Massachusetts Institute of Technology, Department of Biological Engineering, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 85-88). / Resource limitations in bacterial cells can present significant hurdles that preclude correct synthetic circuit behavior. In a simple circuit with one constitutively expressed protein and one protein whose expression is inducible, it has been shown that inducing the expression of the second protein causes a significant decrease in the level of the first. In this thesis, we explore the possibility of reducing the effects of resource limitations by adding a high-gain negative feedback loop to one of the circuits. The loop includes an sRNA construct. We explore different implementations of this circuit and model them mechanistically. Furthermore, we begin physically implementing one of the circuit designs by testing intermediate constructs. Finally, we also explore the hypothesis that exogenous circuits on plasmids compete for a pool of resources that is spatially separated from the resources that the genome utilizes. Through our work, we show results that support the spatial separation hypothesis. / by John Elias Yazbek. / S.M.

Identiferoai:union.ndltd.org:MIT/oai:dspace.mit.edu:1721.1/99056
Date January 2015
CreatorsYazbek, John Elias
ContributorsDomitilla Del Vecchio and Timothy K. Lu., Massachusetts Institute of Technology. Department of Biological Engineering., Massachusetts Institute of Technology. Department of Biological Engineering.
PublisherMassachusetts Institute of Technology
Source SetsM.I.T. Theses and Dissertation
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Format88 pages, application/pdf
RightsMIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission., http://dspace.mit.edu/handle/1721.1/7582

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