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Engineered sensors and genetic regulatory networks for control of cellular metabolism

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dc.contributor Christopher A. Voigt.
dc.contributor Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences.
dc.contributor Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences.
dc.creator Moser, Felix, Ph. D. Massachusetts Institute of Technology
dc.date 2014-04-25T15:49:09Z
dc.date 2014-04-25T15:49:09Z
dc.date 2013
dc.date 2013
dc.identifier http://hdl.handle.net/1721.1/86286
dc.identifier 876050779
dc.description Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2013.
dc.description Cataloged from PDF version of thesis.
dc.description Includes bibliographical references (pages 114-125).
dc.description Complex synthetic genetic programs promise unprecedented control over cellular metabolism and behavior. In this thesis, I describe the design and development of a synthetic genetic program to detect conditions underlying acetate formation in Escherichia coli. To construct this program, I first developed sensors that detected and propagated relevant information into genetic circuits. These sensors include a novel sensor for genotoxic methylation exposure in Saccharomyces cerevisiae and sensors for oxygen, acetate, and glycolytic flux in E. coli. The methylation sensor served to prototype generalizable tuning mechanisms and was tuned to a sensitivity and detection threshold useful for several applications, including the detection of Mel formation in methyl halide transferase-expressing cultures of yeast and the detection of Mel in soil. The sensors for oxygen and acetate were integrated into a program that can uniquely detect acetate formation in anaerobic conditions in E. coli. Finally, to validate their use at higher scales in production strains, the oxygen sensor and two genetic programs were characterized in 10 L fed-batch fermentations. Together, this work demonstrates the characterization of novel genetic elements, their integration into genetic programs, and the validation of those programs at industrially relevant scales.
dc.description by Felix Moser.
dc.description Ph. D.
dc.format 125 pages
dc.format application/pdf
dc.language eng
dc.publisher Massachusetts Institute of Technology
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.
dc.rights http://dspace.mit.edu/handle/1721.1/7582
dc.subject Brain and Cognitive Sciences.
dc.title Engineered sensors and genetic regulatory networks for control of cellular metabolism
dc.type Thesis


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