ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: Biology
- Creators: Wang, Xiao
- Creators: Hurlbut, Ben
Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
Despite the minor differences in the inclusiveness of the word, there is a general assumption among the scientific community that the 'pursuit of knowledge' is the most fundamental element in defining the word 'science'. However, a closer examination of how science is being conducted in modern-day South Korea reveals a value system starkly different from the value of knowledge. By analyzing the political discourse of the South Korean policymakers, mass media, and government documents, this study examines the definition of science in South Korea. The analysis revealed that the Korean science, informed by the cultural, historical, and societal contexts, is largely focused on the values of national economic prosperity, international competitiveness, and international reputation of the country, overshadowing other values like the pursuit of knowledge or even individual rights. The identification of the new value system in South Korean science deviating from the traditional definition of science implies that there must be other definitions of science that also deviates, and that even in the Western world, the definition of science may yield similar deviations upon closer examination. The compatibility of the South Korean brand of science to the international scientific community also implies that a categorical quality is encompassing these different contextual definitions of science.
ContributorsHyun, Byunghun (Author) / Hurlbut, Ben (Thesis advisor) / Maienschein, Jane (Committee member) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2011
Description
Synthetic gene networks have evolved from simple proof-of-concept circuits to
complex therapy-oriented networks over the past fifteen years. This advancement has
greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a
mechanism that cells use to achieve a discrete number of mutually exclusive states in
response to environmental inputs. However, complex contextual connections of gene
regulatory networks in natural settings often impede the experimental establishment of
the function and dynamics of each specific gene network.
In this work, diverse synthetic gene networks are rationally designed and
constructed using well-characterized biological components to approach the cell fate
determination and state transition dynamics in multistable systems. Results show that
unimodality and bimodality and trimodality can be achieved through manipulation of the
signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to
communicate with each other.
Moreover, a synthetic quadrastable circuit is also built and experimentally
demonstrated to have four stable steady states. Experiments, guided by mathematical
modeling predictions, reveal that sequential inductions generate distinct cell fates by
changing the landscape in sequence and hence navigating cells to different final states.
Circuit function depends on the specific protein expression levels in the circuit.
We then establish a protein expression predictor taking into account adjacent
transcriptional regions’ features through construction of ~120 synthetic gene circuits
(operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks.
These combined results illustrate applications of synthetic gene networks to
understand the cell fate determination and state transition dynamics in multistable
systems. A protein-expression predictor is also developed to evaluate and tune circuit
dynamics.
complex therapy-oriented networks over the past fifteen years. This advancement has
greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a
mechanism that cells use to achieve a discrete number of mutually exclusive states in
response to environmental inputs. However, complex contextual connections of gene
regulatory networks in natural settings often impede the experimental establishment of
the function and dynamics of each specific gene network.
In this work, diverse synthetic gene networks are rationally designed and
constructed using well-characterized biological components to approach the cell fate
determination and state transition dynamics in multistable systems. Results show that
unimodality and bimodality and trimodality can be achieved through manipulation of the
signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to
communicate with each other.
Moreover, a synthetic quadrastable circuit is also built and experimentally
demonstrated to have four stable steady states. Experiments, guided by mathematical
modeling predictions, reveal that sequential inductions generate distinct cell fates by
changing the landscape in sequence and hence navigating cells to different final states.
Circuit function depends on the specific protein expression levels in the circuit.
We then establish a protein expression predictor taking into account adjacent
transcriptional regions’ features through construction of ~120 synthetic gene circuits
(operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks.
These combined results illustrate applications of synthetic gene networks to
understand the cell fate determination and state transition dynamics in multistable
systems. A protein-expression predictor is also developed to evaluate and tune circuit
dynamics.
ContributorsWu, Fuqing (Author) / Wang, Xiao (Thesis advisor) / Haynes, Karmella (Committee member) / Marshall, Pamela (Committee member) / Nielsen, David (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2017
Description
A dental exam in twenty-first century America generally includes the taking of radiographs, which are x-ray images of the mouth. These images allow dentists to see structures below the gum line and within the teeth. Having a patient's radiographs on file has become a dental standard of care in many states, but x-rays were only discovered a little over 100 years ago. This research analyzes how and why the x-ray image has become a ubiquitous tool in the dental field. Primary literature written by dentists and scientists of the time shows that the x-ray was established in dentistry by the 1950s. Therefore, this thesis tracks the changes in x-ray technological developments, the spread of information and related safety concerns between 1890 and 1955. X-ray technology went from being an accidental discovery to a device commonly purchased by dentists. X-ray information started out in the form of the anecdotes of individuals and led to the formation of large professional groups. Safety concerns of only a few people later became an important facet of new devices. These three major shifts are described by looking at those who prompted the changes; they fall into the categories of people, technological artifacts and institutions. The x-ray became integrated into dentistry as a product of the work of people such as C. Edmund Kells, a proponent of dental x-rays, technological improvements including faster film speed, and the influence of institutions such as Victor X-Ray Company and the American Dental Association. These changes that resulted established a strong foundation of x-ray technology in dentistry. From there, the dental x-ray developed to its modern form.
ContributorsMartinez, Britta (Author) / Ellison, Karin (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Hurlbut, Ben (Committee member) / Arizona State University (Publisher)
Created2013
Description
Fusion proteins that specifically interact with biochemical marks on chromosomes represent a new class of synthetic transcriptional regulators that decode cell state information rather than deoxyribose nucleic acid (DNA) sequences. In multicellular organisms, information relevant to cell state, tissue identity, and oncogenesis is often encoded as biochemical modifications of histones, which are bound to DNA in eukaryotic nuclei and regulate gene expression states. In 2011, Haynes et al. showed that a synthetic regulator called the Polycomb chromatin Transcription Factor (PcTF), a fusion protein that binds methylated histones, reactivated an artificially-silenced luciferase reporter gene. These synthetic transcription activators are derived from the polycomb repressive complex (PRC) and associate with the epigenetic silencing mark H3K27me3 to reactivate the expression of silenced genes. It is demonstrated here that the duration of epigenetic silencing does not perturb reactivation via PcTF fusion proteins. After 96 hours PcTF shows the strongest reactivation activity. A variant called Pc2TF, which has roughly double the affinity for H3K27me3 in vitro, reactivated the silenced luciferase gene by at least 2-fold in living cells.
ContributorsVargas, Daniel A. (Author) / Haynes, Karmella (Thesis advisor) / Wang, Xiao (Committee member) / Mills, Jeremy (Committee member) / Arizona State University (Publisher)
Created2019
Description
In the US, menstrual education, which provides key information about menstrual hygiene and health to both young girls and boys, historically lacks biologically accurate information about the menstrual cycle and perpetuates harmful perceptions about female reproductive health. When people are unable to differentiate between normal and abnormal menstrual bleeding, based on a lack of quality menstrual education, common gynecological conditions often remain underreported. This raises a question as to how girls’ menstrual education experiences influence the ways in which they perceive normal menstrual bleeding and seek treatment for common abnormalities, such as heavy, painful, or irregular menstrual bleeding. A mixed methods approach allowed evaluation of girls’ abilities to recognize abnormal menstrual bleeding. A literature review established relevant historical and social context on the prevalence and quality of menstrual education in the US. Then, five focus groups, each including five to eight college-aged women, totaling thirty-three participants, allowed for macro-level analysis of current challenges and gaps in knowledge related to menstruation. To better examine the relationship between menstrual education and reproductive health outcomes, twelve semi-structured, one-on-one interviews allowed micro-level analysis. Those interviews consisted of women diagnosed with endometriosis and polycystic ovary syndrome, common gynecological conditions that include abnormal menstrual bleeding. Developing a codebook of definitions and exemplars of significant text segments and applying it to the collected data revealed several themes. For example, mothers, friends, teachers, the Internet, and social media are among the most common sources of information about menstrual hygiene and health. Yet, women reported that those sources of information often echoed stigmatized ideas about menstruation, eliciting feelings of shame and fear. That poor quality of information was instrumental to women’s abilities to detect and report abnormal menstrual bleeding. Women desire and need biologically accurate information about reproductive health, including menstruation and ovulation, fertility, and methods of birth control as treatments for abnormal menstrual bleeding. Unfortunately, menstrual education often leaves girls ill-equipped to identify and seek treatment for common gynecological conditions. Those findings may influence current menstrual education, incorporating biological information and actively dismissing common misconceptions about menstruation that influence stigma.
ContributorsSantora, Emily Katherine (Author) / Maienschein, Jane (Thesis advisor) / Ellison, Karin (Committee member) / Hurlbut, Ben (Committee member) / Arizona State University (Publisher)
Created2021
Description
A notable challenge when assembling synthetic gene circuits is that modularity often fails to function as intended. A crucial underlying reason for this modularity failure is the existence of competition for shared and limited gene expression resources. By designing a synthetic cascading bistable switches (Syn-CBS) circuit in a single strain with two coupled self-activation modules to achieve successive cell fate transitions, nonlinear resource competition within synthetic gene circuits is unveiled. However, in vivo it can be seen that the transition path was redirected with the activation of one switch always prevailing over that of the other, contradictory to coactivation theoretically expected. This behavior is a result of resource competition between genes and follows a ‘winner-takes-all’ rule, where the winner is determined by the relative connection strength between the two modules. Despite investigation demonstrating that resource competition between gene modules can significantly alter circuit deterministic behaviors, how resource competition contributes to gene expression noise and how this noise can be controlled is still an open issue of fundamental importance in systems biology and biological physics. By utilizing a two-gene circuit, the effects of resource competition on protein expression noise levels can be closely studied. A surprising double-edged role is discovered: the competition for these resources decreases noise while the constraint on resource availability adds its own term of noise into the system, denoted “resource competitive” noise. Noise reduction effects are then studied using orthogonal resources. Results indicate that orthogonal resources are a good strategy for eliminating the contribution of resource competition to gene expression noise.
Noise propagation through a cascading circuit has been considered without resource competition. It has been noted that the noise from upstream genes can be transmitted downstream. However, resource competition’s effects on this cascading noise have yet to be studied. When studied, it is found that resource competition can induce stochastic state
switching and perturb noise propagation. Orthogonal resources can remove some of the resource competitive behavior and allow for a system with less noise.
ContributorsGoetz, Hanah Elizabeth (Author) / Tian, Xiaojun (Thesis advisor) / Wang, Xiao (Committee member) / Lai, Ying-Cheng (Committee member) / Arizona State University (Publisher)
Created2022