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Signal Transduction with Hybridization Chain Reactions

Citation

Sternberg, Jonathan Ben-Zion (2013) Signal Transduction with Hybridization Chain Reactions. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z90Z719Z. https://resolver.caltech.edu/CaltechTHESIS:06072013-170244348

Abstract

Some of the most exciting developments in the field of nucleic acid engineering include the utilization of synthetic nucleic acid molecular devices as gene regulators, as disease marker detectors, and most recently, as therapeutic agents. The common thread between these technologies is their reliance on the detection of specific nucleic acid input markers to generate some desirable output, such as a change in the copy number of an mRNA (for gene regulation), a change in the emitted light intensity (for some diagnostics), and a change in cell state within an organism (for therapeutics). The research presented in this thesis likewise focuses on engineering molecular tools that detect specific nucleic acid inputs, and respond with useful outputs.

Four contributions to the field of nucleic acid engineering are presented: (1) the construction of a single nucleotide polymorphism (SNP) detector based on the mechanism of hybridization chain reaction (HCR); (2) the utilization of a single-stranded oligonucleotide molecular Scavenger as a means of enhancing HCR selectivity; (3) the implementation of Quenched HCR, a technique that facilitates transduction of a nucleic acid chemical input into an optical (light) output, and (4) the engineering of conditional probes that function as sequence transducers, receiving target signal as input and providing a sequence of choice as output. These programmable molecular systems are conceptually well-suited for performing wash-free, highly selective rapid genotyping and expression profiling in vitro, in situ, and potentially in living cells.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:diagnostic; diagnostics; triggered; amplification; isothermal; enzyme-free
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Bioengineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Pierce, Niles/ A
Thesis Committee:
  • Tirrell, David A. (chair)
  • Fraser, Scott E.
  • Elowitz, Michael B.
  • Pierce, Niles A.
Defense Date:22 May 2013
Record Number:CaltechTHESIS:06072013-170244348
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:06072013-170244348
DOI:10.7907/Z90Z719Z
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7874
Collection:CaltechTHESIS
Deposited By: Jonathan Sternberg
Deposited On:19 Jan 2016 21:56
Last Modified:04 Oct 2019 00:02

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