Date of Award

Spring 1-1-2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Anushree Chatterjee

Second Advisor

Robert T. Batey

Third Advisor

Stephanie J. Bryant

Fourth Advisor

Robin D. Dowell

Fifth Advisor

Jerome M. Fox

Abstract

Microorganisms inhabit every extreme location of our planet. In their journey through the ages, they have been able to incredibly adapt to a myriad of different environmental conditions. A key mechanism for their success has been their ability to respond to environmental and nutritional changes through regulatory programs primarily encoded at the transcriptional level. This adaptability to new environments is what encourages scientists to believe in engineering a biological revolution that will transform our lives due to its potential to result in innovative approaches for bioremediation, sustainable energy production, and biomedical therapies. This thesis explores the potential of the phenomenon of Transcriptional Interference with the goal of being able to create genetic devices that act as higher-order genetic switches. I accomplished this objective via three distinct and complementary aims: creating a complete computational model that takes into consideration the three layers of regulation that might be present in convergent arrangements of promoters, experimentally studying protein expression from sets of convergent promoters, and building a library of constructs subjected to Transcriptional Interference that act like logic gates devices. Thus, this thesis is an effort to demonstrate that, besides the canonical transcription factor regulation, the process of transcription elongation can also be engineered to regulate gene expression.

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