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- Creators: Barrett, The Honors College
Description
The principle of Darwinian evolution has been applied in the laboratory to nucleic acid molecules since 1990, and led to the emergence of in vitro evolution technique. The methodology of in vitro evolution surveys a large number of different molecules simultaneously for a pre-defined chemical property, and enrich for molecules with the particular property. DNA and RNA sequences with versatile functions have been identified by in vitro selection experiments, but many basic questions remain to be answered about how these molecules achieve their functions. This dissertation first focuses on addressing a fundamental question regarding the molecular recognition properties of in vitro selected DNA sequences, namely whether negatively charged DNA sequences can be evolved to bind alkaline proteins with high specificity. We showed that DNA binders could be made, through carefully designed stringent in vitro selection, to discriminate different alkaline proteins. The focus of this dissertation is then shifted to in vitro evolution of an artificial genetic polymer called threose nucleic acid (TNA). TNA has been considered a potential RNA progenitor during early evolution of life on Earth. However, further experimental evidence to support TNA as a primordial genetic material is lacking. In this dissertation we demonstrated the capacity of TNA to form stable tertiary structure with specific ligand binding property, which suggests a possible role of TNA as a pre-RNA genetic polymer. Additionally, we discussed the challenges in in vitro evolution for TNA enzymes and developed the necessary methodology for future TNA enzyme evolution.
ContributorsYu, Hanyang (Author) / Chaput, John C (Thesis advisor) / Chen, Julian (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
The production of monomer compounds for synthesizing plastics has to date been largely restricted to the petroleum-based chemical industry and sugar-based microbial fermentation, limiting its sustainability and economic feasibility. Cyanobacteria have, however, become attractive microbial factories to produce renewable fuels and chemicals directly from sunlight and CO2. To explore the feasibility of photosynthetic production of (S)- and (R)-3-hydroxybutyrate (3HB), building-block monomers for synthesizing the biodegradable plastics polyhydroxyalkanoates and precursors to fine chemicals, synthetic metabolic pathways have been constructed, characterized and optimized in the cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis 6803). Both types of 3HB molecules were produced and readily secreted from Synechocystis cells without over-expression of transporters. Additional inactivation of the competing PHB biosynthesis pathway further promoted the 3HB production. Analysis of the intracellular acetyl-CoA and anion concentrations in the culture media indicated that the phosphate consumption during the photoautotrophic growth and the concomitant elevated acetyl-CoA pool acted as a key driving force for 3HB biosynthesis in Synechocystis. Fine-tuning of the gene expression levels via strategies, including tuning gene copy numbers, promoter engineering and ribosome binding site optimization, proved critical to mitigating metabolic bottlenecks and thus improving the 3HB production. One of the engineered Synechocystis strains, namely R168, was able to produce (R)-3HB to a cumulative titer of ~1600 mg/L, with a peak daily productivity of ~200 mg/L, using light and CO2 as the sole energy and carbon sources, respectively. Additionally, in order to establish a high-efficiency transformation protocol in cyanobacterium Synechocystis 6803, methyltransferase-encoding genes were cloned and expressed to pre-methylate the exogenous DNA before Synechocystis transformation. Eventually, the transformation efficiency was increased by two orders of magnitude in Synechocystis. This research has demonstrated the use of cyanobacteria as cell factories to produce 3HB directly from light and CO2, and developed new synthetic biology tools for cyanobacteria.
ContributorsWang, Bo (Author) / Meldrum, Deirdre R (Thesis advisor) / Zhang, Weiwen (Committee member) / Sandrin, Todd R. (Committee member) / Nielsen, David R (Committee member) / Arizona State University (Publisher)
Created2014
Description
Synthetic biology is constantly evolving as new ideas are incorporated into this increasingly flexible field. It incorporates the engineering of life with standard genetic parts and methods; new organisms with new genomes; expansion of life to include new components, capabilities, and chemistries; and even completely synthetic organisms that mimic life while being composed of non-living matter. We have introduced a new paradigm of synthetic biology that melds the methods of in vitro evolution with the goals and philosophy of synthetic biology. The Family B proteins represent the first de novo evolved natively folded proteins to be developed with increasingly powerful tools of molecular evolution. These proteins are folded and functional, composed of the 20 canonical amino acids, and in many ways resemble natural proteins. However, their evolutionary history is quite different from natural proteins, as it did not involve a cellular environment. In this study, we examine the properties of DX, one of the Family B proteins that have been evolutionarily optimized for folding stability. Described in chapter 2 is an investigation into the primitive catalytic properties of DX, which seems to have evolved a serendipitous ATPase activity in addition to its selected ATP binding activity. In chapters 3 and 4 we express the DX gene in E. coli cells and observe massive changes in cell morphology, biochemistry, and life cycle. Exposure to DX activates several defense systems in E. coli, including filamentation, cytoplasmic segregation, and reversion to a viable but non-culturable state. We examined these phenotypes in detail and present a model that accounts for how DX causes such a rearrangement of the cell.
ContributorsStomel, Joshua (Author) / Chaput, John C (Thesis advisor) / Korch, Shaleen (Committee member) / Roberson, Robert (Committee member) / Ghirlanda, Gionvanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
Advances in chemical synthesis have enabled new lines of research with unnatural genetic polymers whose modified bases or sugar-phosphate backbones have potential therapeutic and biotechnological applications. Maximizing the potential of these synthetic genetic systems requires inventing new molecular biology tools that can both generate and faithfully replicate unnatural polymers of significant length. Threose nucleic acid (TNA) has received significant attention as a complete replication system has been developed by engineering natural polymerases to broaden their substrate specificity. The system, however, suffers from a high mutational load reducing its utility. This thesis will cover the development of two new polymerases capable of transcribing and reverse transcribing TNA polymers with high efficiency and fidelity. The polymerases are identified using a new strategy wherein gain-of-function mutations are sampled in homologous protein architectures leading to subtle optimization of protein function. The new replication system has a fidelity that supports the propagation of genetic information enabling in vitro selection of functional TNA molecules. TNA aptamers to human alpha-thrombin are identified and demonstrated to have superior stability compared to DNA and RNA in biologically relevant conditions. This is the first demonstration that functional TNA molecules have potential in biotechnology and molecular medicine.
ContributorsDunn, Matthew Ryan (Author) / Chaput, John C (Thesis advisor) / LaBaer, Joshua (Committee member) / Lake, Douglas (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2015
Description
For as long as humans have been working, they have been looking for ways to get that work done better, faster, and more efficient. Over the course of human history, mankind has created innumerable spectacular inventions, all with the goal of making the economy and daily life more efficient. Today, innovations and technological advancements are happening at a pace like never seen before, and technology like automation and artificial intelligence are poised to once again fundamentally alter the way people live and work in society. Whether society is prepared or not, robots are coming to replace human labor, and they are coming fast. In many areas artificial intelligence has disrupted entire industries of the economy. As people continue to make advancements in artificial intelligence, more industries will be disturbed, more jobs will be lost, and entirely new industries and professions will be created in their wake. The future of the economy and society will be determined by how humans adapt to the rapid innovations that are taking place every single day. In this paper I will examine the extent to which automation will take the place of human labor in the future, project the potential effect of automation to future unemployment, and what individuals and society will need to do to adapt to keep pace with rapidly advancing technology. I will also look at the history of automation in the economy. For centuries humans have been advancing technology to make their everyday work more productive and efficient, and for centuries this has forced humans to adapt to the modern technology through things like training and education. The thesis will additionally examine the ways in which the U.S. education system will have to adapt to meet the demands of the advancing economy, and how job retraining programs must be modernized to prepare workers for the changing economy.
ContributorsCunningham, Reed P. (Author) / DeSerpa, Allan (Thesis director) / Haglin, Brett (Committee member) / School of International Letters and Cultures (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The original version of Helix, the one I pitched when first deciding to make a video game
for my thesis, is an action-platformer, with the intent of metroidvania-style progression
and an interconnected world map.
The current version of Helix is a turn based role-playing game, with the intent of roguelike
gameplay and a dark fantasy theme. We will first be exploring the challenges that came
with programming my own game - not quite from scratch, but also without a prebuilt
engine - then transition into game design and how Helix has evolved from its original form
to what we see today.
for my thesis, is an action-platformer, with the intent of metroidvania-style progression
and an interconnected world map.
The current version of Helix is a turn based role-playing game, with the intent of roguelike
gameplay and a dark fantasy theme. We will first be exploring the challenges that came
with programming my own game - not quite from scratch, but also without a prebuilt
engine - then transition into game design and how Helix has evolved from its original form
to what we see today.
ContributorsDiscipulo, Isaiah K (Author) / Meuth, Ryan (Thesis director) / Kobayashi, Yoshihiro (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
RecyclePlus is an iOS mobile application that allows users to be knowledgeable in the realms of sustainability. It gives encourages users to be environmental responsible by providing them access to recycling information. In particular, it allows users to search up certain materials and learn about its recyclability and how to properly dispose of the material. Some searches will show locations of facilities near users that collect certain materials and dispose of the materials properly. This is a full stack software project that explores open source software and APIs, UI/UX design, and iOS development.
ContributorsTran, Nikki (Author) / Ganesh, Tirupalavanam (Thesis director) / Meuth, Ryan (Committee member) / Watts College of Public Service & Community Solut (Contributor) / Department of Information Systems (Contributor) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Pandora is a play exploring our relationship with gendered technology through the lens of artificial intelligence. Can women be subjective under patriarchy? Do robots who look like women have subjectivity? Hoping to create a better version of ourselves, The Engineer must navigate the loss of her creation, and Pandora must navigate their new world. The original premiere run was March 27-28, 2018, original cast: Caitlin Andelora, Rikki Tremblay, and Michael Tristano Jr.
ContributorsToye, Abigail Elizabeth (Author) / Linde, Jennifer (Thesis director) / Abele, Kelsey (Committee member) / Department of Information Systems (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This paper details the specification and implementation of a single-machine blockchain simulator. It also includes a brief introduction on the history & underlying concepts of blockchain, with explanations on features such as decentralization, openness, trustlessness, and consensus. The introduction features a brief overview of public interest and current implementations of blockchain before stating potential use cases for blockchain simulation software. The paper then gives a brief literature review of blockchain's role, both as a disruptive technology and a foundational technology. The literature review also addresses the potential and difficulties regarding the use of blockchain in Internet of Things (IoT) networks, and also describes the limitations of blockchain in general regarding computational intensity, storage capacity, and network architecture. Next, the paper gives the specification for a generic blockchain structure, with summaries on the behaviors and purposes of transactions, blocks, nodes, miners, public & private key cryptography, signature validation, and hashing. Finally, the author gives an overview of their specific implementation of the blockchain using C/C++ and OpenSSL. The overview includes a brief description of all the classes and data structures involved in the implementation, including their function and behavior. While the implementation meets the requirements set forward in the specification, the results are more qualitative and intuitive, as time constraints did not allow for quantitative measurements of the network simulation. The paper concludes by discussing potential applications for the simulator, and the possibility for future hardware implementations of blockchain.
ContributorsRauschenbach, Timothy Rex (Author) / Vrudhula, Sarma (Thesis director) / Nakamura, Mutsumi (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
The purpose of our research was to develop recommendations and/or strategies for Company A's data center group in the context of the server CPU chip industry. We used data collected from the International Data Corporation (IDC) that was provided by our team coaches, and data that is accessible on the internet. As the server CPU industry expands and transitions to cloud computing, Company A's Data Center Group will need to expand their server CPU chip product mix to meet new demands of the cloud industry and to maintain high market share. Company A boasts leading performance with their x86 server chips and 95% market segment share. The cloud industry is dominated by seven companies Company A calls "The Super 7." These seven companies include: Amazon, Google, Microsoft, Facebook, Alibaba, Tencent, and Baidu. In the long run, the growing market share of the Super 7 could give them substantial buying power over Company A, which could lead to discounts and margin compression for Company A's main growth engine. Additionally, in the long-run, the substantial growth of the Super 7 could fuel the development of their own design teams and work towards making their own server chips internally, which would be detrimental to Company A's data center revenue. We first researched the server industry and key terminology relevant to our project. We narrowed our scope by focusing most on the cloud computing aspect of the server industry. We then researched what Company A has already been doing in the context of cloud computing and what they are currently doing to address the problem. Next, using our market analysis, we identified key areas we think Company A's data center group should focus on. Using the information available to us, we developed our strategies and recommendations that we think will help Company A's Data Center Group position themselves well in an extremely fast growing cloud computing industry.
ContributorsJurgenson, Alex (Co-author) / Nguyen, Duy (Co-author) / Kolder, Sean (Co-author) / Wang, Chenxi (Co-author) / Simonson, Mark (Thesis director) / Hertzel, Michael (Committee member) / Department of Finance (Contributor) / Department of Management (Contributor) / Department of Information Systems (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / School of Accountancy (Contributor) / WPC Graduate Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05