Matching Items (312)
Filtering by
- All Subjects: Business Administration
- Creators: Arizona State University
- Creators: Gu, Bin
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
A major goal of synthetic biology is to recapitulate emergent properties of life. Despite a significant body of work, a longstanding question that remains to be answered is how such a complex system arose? In this dissertation, synthetic nucleic acid molecules with alternative sugar-phosphate backbones were investigated as potential ancestors of DNA and RNA. Threose nucleic acid (TNA) is capable of forming stable helical structures with complementary strands of itself and RNA. This provides a plausible mechanism for genetic information transfer between TNA and RNA. Therefore TNA has been proposed as a potential RNA progenitor. Using molecular evolution, functional sequences were isolated from a pool of random TNA molecules. This implicates a possible chemical framework capable of crosstalk between TNA and RNA. Further, this shows that heredity and evolution are not limited to the natural genetic system based on ribofuranosyl nucleic acids. Another alternative genetic system, glycerol nucleic acid (GNA) undergoes intrasystem pairing with superior thermalstability compared to that of DNA. Inspired by this property, I demonstrated a minimal nanostructure composed of both left- and right-handed mirro image GNA. This work suggested that GNA could be useful as promising orthogonal material in structural DNA nanotechnology.
ContributorsZhang, Su (Author) / Chaut, John C (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2011
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
Currently in synthetic biology only the Las, Lux, and Rhl quorum sensing pathways have been adapted for broad engineering use. Quorum sensing allows a means of cell to cell communication in which a designated sender cell produces quorum sensing molecules that modify gene expression of a designated receiver cell. While useful, these three quorum sensing pathways exhibit a nontrivial level of crosstalk, hindering robust engineering and leading to unexpected effects in a given design. To address the lack of orthogonality among these three quorum sensing pathways, previous scientists have attempted to perform directed evolution on components of the quorum sensing pathway. While a powerful tool, directed evolution is limited by the subspace that is defined by the protein. For this reason, we take an evolutionary biology approach to identify new orthogonal quorum sensing networks and test these networks for cross-talk with currently-used networks. By charting characteristics of acyl homoserine lactone (AHL) molecules used across quorum sensing pathways in nature, we have identified favorable candidate pathways likely to display orthogonality. These include Aub, Bja, Bra, Cer, Esa, Las, Lux, Rhl, Rpa, and Sin, which we have begun constructing and testing. Our synthetic circuits express GFP in response to a quorum sensing molecule, allowing quantitative measurement of orthogonality between pairs. By determining orthogonal quorum sensing pairs, we hope to identify and adapt novel quorum sensing pathways for robust use in higher-order genetic circuits.
ContributorsMuller, Ryan (Author) / Haynes, Karmella (Thesis director) / Wang, Xiao (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
One of the primary bottlenecks to chemical production in biological organisms is the toxicity of the chemical. Overexpression of efflux pumps has been shown to increase tolerance to aromatic compounds such as styrene and styrene oxide. Tight control of pump expression is necessary to maximize titers and prevent excessive strain on the cells. This study aimed to identify aromatic-sensitive native promoters and heterologous biosensors for construction of closed-loop control of efflux pump expression in E. coli. Using a promoter library constructed by Zaslaver et al., activation was measured through GFP output. Promoters were evaluated for their sensitivity to the addition of one of four aromatic compounds, their "leaking" of signal, and their induction threshold. Out of 43 targeted promoters, 4 promoters (cmr, mdtG, yahN, yajR) for styrene oxide, 2 promoters (mdtG, yahN) for styrene, 0 promoters for 2-phenylethanol, and 1 promoter for phenol (pheP) were identified as ideal control elements in aromatic bioproduction. In addition, a series of three biosensors (NahR, XylS, DmpR) known to be inducible by other aromatics were screened against styrene oxide, 2-phenylethanol, and phenol. The targeted application of these biosensors is aromatic-induced activation of linked efflux pumps. All three biosensors responded strongly in the presence of styrene oxide and 2-phenylethanol, with minor activation in the presence of phenol. Bioproduction of aromatics continues to gain traction in the biotechnology industry, and the continued discovery of aromatic-inducible elements will be essential to effective pathway control.
ContributorsXu, Jimmy (Author) / Nielsen, David (Thesis director) / Wang, Xuan (Committee member) / School of Life Sciences (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Synthetic biology is an emerging engineering disciple, which designs and controls biological systems for creation of materials, biosensors, biocomputing, and much more. To better control and engineer these systems, modular genetic components which allow for highly specific and high dynamic range genetic regulation are necessary. Currently the field struggles to demonstrate reliable regulators which are programmable and specific, yet also allow for a high dynamic range of control. Inspired by the characteristics of the RNA toehold switch in E. coli, this project attempts utilize artificial introns and complementary trans-acting RNAs for gene regulation in a eukaryote host, S. cerevisiae. Following modification to an artificial intron, splicing control with RNA hairpins was demonstrated. Temperature shifts led to increased protein production likely due to increased splicing due to hairpin loosening. Progress is underway to demonstrate trans-acting RNA interaction to control splicing. With continued development, we hope to provide a programmable, specific, and effective means for translational gene regulation in S. cerevisae.
ContributorsDorr, Brandon Arthur (Author) / Wang, Xiao (Thesis director) / Green, Alexander (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
p-Coumaric acid is used in the food, pharmaceutical, and cosmetic industries due to its versatile properties. While prevalent in nature, harvesting the compound from natural sources is inefficient, requiring large quantities of producing crops and numerous extraction and purification steps. Thus, the large-scale production of the compound is both difficult and costly. This research aims to produce p-coumarate directly from renewable and sustainable glucose using a co-culture of Yeast and E. Coli. Methods used in this study include: designing optimal media for mixed-species microbial growth, genetically engineering both strains to build the production pathway with maximum yield, and analyzing the presence of p-Coumarate and its pathway intermediates using High Performance Liquid Chromatography (HPLC). To date, the results of this project include successful integration of C4H activity into the yeast strain BY4741 ∆FDC1, yielding a strain that completely consumed trans-cinnamate (initial concentration of 50 mg/L) and produced ~56 mg/L p-coumarate, a resting cell assay of the co-culture that produced 0.23 mM p-coumarate from an initial L-Phenylalanine concentration of 1.14 mM, and toxicity tests that confirmed the toxicity of trans-cinnamate to yeast for concentrations above ~50 mg/L. The hope for this project is to create a feasible method for producing p-Coumarate sustainably.
ContributorsJohnson, Kaleigh Lynnae (Author) / Nielsen, David (Thesis director) / Thompson, Brian (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
As more goods and processes are digitalized and available online, supply chains began to transact digitalized goods and processes that do not involve physical distribution. This dissertation defines this type of supply chain as “digital supply chain” and aims to extend the knowledge for better management of digital supply chains. Digital goods are granularly codifiable and easily duplicatable, and digital processes are less constrained by time and distance. For these reasons, compared to conventional supply chains, digital supply chains have the following features: the delivery of goods is faster; the innovation cycle is shorter; post-sales product modification is easier; and customers switch between the providers of alternative goods more frequently and easily. Given these traits of digital supply chains, this dissertation focuses on the timing of firms’ actions and their consequences under the consideration of dynamic interactions with competitors, customers, and business environments. The dissertation consists of four chapters. Chapter 1 briefly introduces the concept and issues of digital supply chains. Chapter 2 investigates how a service provider’s failure leads to a competing firm’s responsive innovation in the innovation-driven digital service industry. Chapter 3 demonstrates the relationship between market environments and innovation cycles in the innovation-driven digital service industry. Lastly, Chapter 4 studies evolving supply chain cyber-vulnerability from the perspective of agency theory.
ContributorsJeong, Seongkyoon (Author) / Choi, Thomas T (Thesis advisor) / Oke, Adegoke A (Committee member) / Dooley, Kevin K (Committee member) / Arizona State University (Publisher)
Created2022
Description政府引导基金自诞生至今，始终处于管理模式的摸索状态。本文试图从公司治理的角度分析不同利益方（政府、社会出资人以及管理人）之间的博弈关系以及其对引导基金投资效果的影响。政府引导基金的注册数量和规模在过去十几年中得到了快速显著的发展。从引导基金设立的政府行政层级来看，地县级政府设立基金是引导基金出资中的绝对主力。本文拟深入研究地县级政府引导基金的运作模式，尝试探索其治理结构与投资效果。
目前，引导基金的运作模式仍然处于摸索阶段，论文试图对引导基金若干个指标做出客观比较，分析政府参与度对资金投资效果的影响，希望对未来引导基金的设立模式选择提供有力的理论基础。为实现较好的研究效果，论文选择了某经济发达的地级市的样本进行了研究，该市的政府引导私募股权基金发展程度相对较高，市本级以及区县级均有较多的政府引导私募股权基金，该市范围政府引导私募股权基金可研究价值相对较高。在样本选择方面，论文将采样某市及所辖区县政府直接出资基金十六只，针对其参与设立的直投基金以及直接投资项目进行分析。同时，论文还总正反两个方面选择了两个经典案例进行详细剖析。
论文发现，市场化运作程度越低，引导基金所期望实现的目标效果相对不理想，投资效果越差。政府在决策中所占比重越高，形成的投资决策对于项目成长性判断的准确度越差，对地方经济社会发展的综合贡献越低。然而，纯粹的商业运作，无法实现引导基金所承担的社会使命。对不同的资金诉求导致的投资要求在不同的决策层级实现，通过政府或其代表出资方对管理方以协议约束的方式保证其投资行为而不再进行对单个项目进行价值判断，是有效实现引导诉求和专业判断兼顾的引导基金管理模式。
论文建议，在经济相对发达地区，政府引导基金应该积极采用市场化运作模式，在现有可选择的模式中，政府引导基金以LP身份且获取咨询委角色，从外部监察约束角度对基金进行投资引导的模式为最佳选择。
ContributorsWu, Di (Author) / Pei, Ker-Wei (Thesis advisor) / Wu, Fei (Thesis advisor) / Zhu, David (Committee member) / Arizona State University (Publisher)
Created2022
Description本文对中国制药企业并购溢价影响因素进行了研究，提出了对制药企业并购非常重要的两个新的影响因素：可生产药品批文和在研新药批文。本文以2011年1月—2019年12月间我国制药行业上市公司并购事件为样本，对在研新药和可生产药品批文的价值从四个维度度量：是否有在研新药和可生产药品批文；在研新药数量及可生产药品批文数量；根据创新药和仿制药两个类别进行细分；标的企业所拥有的在研新药和可生产药品批文的市场价值。论文发现药品批文对企业并购溢价的影响不是很显著。进一步的，本文探究了药品批文对主并企业的对被并购公司的估值的影响。实证结果表明，我国制药企业在并购估值时确实会考虑到在研新药和可生产药品批文的价值。本文还发现对于可生产药品来说，相对创新药，被并购公司持有的仿制药批文影响更显著。而对于在研新药来说，主并企业更看重在研的创新药，在研仿制药对并购估值的影响不大。最后，本文选取了两个代表性案例进一步分析和探讨药品批文对企业并购的影响。
ContributorsYe, Tao (Author) / Shen, Wei (Thesis advisor) / Chang, Chun (Thesis advisor) / Jiang, Zhan (Committee member) / Gu, Bin (Committee member) / Arizona State University (Publisher)
Created2022