Programming Molecular Devices using Nucleic Acid Hairpins

Nucleic Acid hairpins have been a subject of study for the last four decades. They are composed of single strand that is

hybridized to itself, and the central section forming an unhybridized loop. In nature, they stabilize single stranded RNA, serve as nucleation

sites for RNA folding, protein recognition signals, mRNA localization and regulation of mRNA degradation. On the other hand,

DNA hairpins in biological contexts have been studied with respect to forming cruciform structures that can regulate gene expression.

The use of DNA hairpins as fuel for synthetic molecular devices, including locomotion, was proposed and experimental demonstrated in 2003. They

were interesting because they bring to the table an on-demand energy/information supply mechanism.

The energy/information is hidden (from hybridization) in the hairpin’s loop, until required.

The energy/information is harnessed by opening the stem region, and exposing the single stranded loop section.

The loop region is now free for possible hybridization and help move the system into a thermodynamically favourable state.

The hidden energy and information coupled with

programmability provides another functionality, of selectively choosing what reactions to hide and

what reactions to allow to proceed, that helps develop a topological sequence of events.

Hairpins have been utilized as a source of fuel for many different DNA devices. In this thesis, we program four different

molecular devices using DNA hairpins, and experimentally validate them in the

laboratory. 1) The first device: A

novel enzyme-free autocatalytic self-replicating system composed entirely of DNA that operates isothermally. 2) The second

device: Time-Responsive Circuits using DNA have two properties: a) asynchronous: the final output is always correct

regardless of differences in the arrival time of different inputs.

b) renewable circuits which can be used multiple times without major degradation of the gate motifs

(so if the inputs change over time, the DNA-based circuit can re-compute the output correctly based on the new inputs).

3) The third device: Activatable tiles are a theoretical extension to the Tile assembly model that enhances

its robustness by protecting the sticky sides of tiles until a tile is partially incorporated into a growing assembly.

4) The fourth device: Controlled Amplification of DNA catalytic system: a device such that the amplification

of the system does not run uncontrollably until the system runs out of fuel, but instead achieves a finite

amount of gain.

Nucleic acid circuits with the ability

to perform complex logic operations have many potential practical applications, for example the ability to achieve point of care diagnostics.

We discuss the designs of our DNA Hairpin molecular devices, the results we have obtained, and the challenges we have overcome

to make these truly functional.

Phase Locked Loop and Modulo Games, The Dogma Loops; and “Finding Ibrida”

This dissertation consists of two independent musical compositions and an article detailing the process of the design and assembly of an electric guitar with particular emphasis on the carefully curated suite of embedded effects.

The first piece, 'Phase Locked Loop and Modulo Games' is scored for electric guitar and a single echo of equal volume less than a beat away. One could think of the piece as a 15 minute canon at the unison at the dotted eighth note (or at times the quarter or triplet-quarter), however the compositional motivation is more about weaving a composite texture between the guitar and its echo that is, while in theory extremely contrapuntal, in actuality is simply a single [superhuman] melodic line.

The second piece, 'The Dogma Loops' picks up a few compositional threads left by ‘Phase Locked Loop’ and weaves them into an entirely new tapestry. 'Phase Locked Loop' is motivated by the creation of a complex musical composite that is for the most part electronically transparent. 'The Dogma Loops' questions that same notion of composite electronic complexity by essentially asking a question: "what are the inputs to an interactive electronic system that create the most complex outputs via the simplest musical means possible?"

'The Dogma Loops' is scored for Electric Guitar (doubling on Ukulele), Violin and Violoncello. All of the principal instruments require an electronic pickup (except the Uke). The work is in three sections played attacca; [Automation Games], [Point of Origin] and [Cloning Vectors].

The third and final component of the document is the article 'Finding Ibrida.' This article details the process of the design and assembly of an electric guitar with integrated effects, while also providing the deeper context (conceptual and technical) which motivated the efforts and informed the challenges to hybridize the various technologies (tubes, transistors, digital effects and a microcontroller subsystem). The project was motivated by a desire for rigorous technical and hands-on engagement with analog signal processing as applied to the electric guitar. ‘Finding Ibrida’ explores sound, some myths and lore of guitar tech and the history of electric guitar distortion and its culture of sonic exploration.