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Deciphering Regulation in Escherichia coli: From Genes to Genomes

Citation

Beeler, Suzannah Michelle (2022) Deciphering Regulation in Escherichia coli: From Genes to Genomes. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/p3rg-m937. https://resolver.caltech.edu/CaltechTHESIS:08182021-053622635

Abstract

Advances in DNA sequencing have revolutionized our ability to read genomes. However, even in the most well-studied of organisms, the bacterium Escherichia coli, for ≈ 65% of promoters we remain ignorant of their regulation. Until we crack this regulatory Rosetta Stone, efforts to read and write genomes will remain haphazard. We introduce a new method, Reg-Seq, that links massively-parallel reporter assays with mass spectrometry to produce a base pair resolution dissection of more than 100 E. coli promoters in 12 growth conditions. We demonstrate that the method recapitulates known regulatory information. Then, we examine regulatory architectures for more than 80 promoters which previously had no known regulatory information. In many cases, we also identify which transcription factors mediate their regulation. This method clears a path for highly multiplexed investigations of the regulatory genome of model organisms, with the potential of moving to an array of microbes of ecological and medical relevance.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Escherichia coli; gene regulation; transcription factors; massively parallel reporter assays
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Phillips, Robert B.
Thesis Committee:
  • Rothenberg, Ellen V. (chair)
  • Goentoro, Lea A.
  • Thomson, Matthew
  • Phillips, Robert B.
Defense Date:22 July 2021
Non-Caltech Author Email:sbeeler15 (AT) gmail.com
Record Number:CaltechTHESIS:08182021-053622635
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:08182021-053622635
DOI:10.7907/p3rg-m937
Related URLs:
URLURL TypeDescription
https://www.doi.org/10.7554/eLife.55308DOIArticle adapted for Chapter 2.
https://github.com/RPGroup-PBoC/Reg-Seq2/releases/tag/twist_orderOtherGithub repository, as referenced in Chapter 3.
ORCID:
AuthorORCID
Beeler, Suzannah Michelle0000-0002-1930-4827
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14327
Collection:CaltechTHESIS
Deposited By: Suzannah Beeler
Deposited On:23 Aug 2021 15:37
Last Modified:29 Oct 2021 22:42

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