Title:
DEVELOPING A TRANSCRIPTIONAL PROGRAMMING EDIFICE USING SYSTEMS OF ENGINEERED TRANSCRIPTION FACTORS

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Authors
Rondon, Ronald Enrique
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Wilson, Corey J.
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Abstract
The control of gene expression is an important tool for metabolic engineering, biomedicine, and biomanufacturing. Currently, the field of Synthetic Biology is limited by the ability to construct synthetic, multi-input promoters, which is constrained by the number of unique transcription factors (or systems of transcription factors) that can simultaneously regulate a single promoter. This engineering constraint is an obstacle to because it limits the computational capacity of engineered gene circuits. One solution to the problem is to develop a scalable collection of novel transcription factors that are not only orthogonal to native cellular environments but can also work as systems to confer combinatorial logic over gene production. We posit that the structure of the Lactose Repressor (LacI) - a canonical transcription factor and a hallmark of allosteric communication - is an ideal template to be used for the development of a large system of transcription factors with alternate DNA recognition and ligand binding abilities. This collection of LacI inspired transcription factors can then be leveraged to create complex multiple signal logical operations that offer scalable control of synthetic gene networks. The work presented throughout this study yields a significant enhancement in biological computing capacity, which enables the construction of synthetic regulatory networks approaching the scale of natural networks in bacteria.
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Date Issued
2021-01-08
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Dissertation
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