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: Hall, Sharon
- Creators: Wang, Xiao
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
Coal bed natural gas (CBNG) production has become a significant contribution to the nation's energy supply. Large volumes of water are generated as a byproduct of CBNG extraction, of which this "product water" is relatively high in sodium. High sodicity reduces water quality and limits environmentally compliant disposal options for producers. Crop irrigation with CBNG product water complies with state and federal laws and is a disposal method that also provides a beneficial use to private landowners. However, this disposal method typically requires gypsum and sulfur soil amendments due to the high levels of sodium in the water, which can reduce soil infiltration and hydraulic conductivity. In this study, I tested a new product called Salt Extractor that was marketed to CBNG producers to ameliorate the negative effects of high sodicity. The experiment was conducted in the Powder River Basin of Wyoming. I used a random block design to compare the soil and vegetation properties of plots following application with CBNG product water and treatments of either Salt Extractor, gypsum and sulfur (conventional), or no treatment (control). Data was analyzed by comparing the amount of change between treatments after watering. Results demonstrated the known ability of gypsum and sulfur to lower the relative sodicity of the soil. Plots treated with Salt Extractor, however, did not improve relative levels of sodicity and exhibited no favorable benefits to vegetation.
ContributorsAdams, Shelly (Author) / Hall, Sharon (Thesis advisor) / Chew, Matt (Committee member) / Stromberg, Juliet (Committee member) / Arizona State University (Publisher)
Created2011
Description
Aboveground net primary production (ANPP) and belowground net primary production (BNPP) may not be influenced equally by the same factors in arid grasslands. Precipitation is known to affect ANPP and BNPP, while soil fauna such as nematodes affect the BNPP through herbivory and predation. This study on black grama grass (Bouteloua eriopoda) in the Chihuahuan Desert investigates the effects of precipitation and nematode presence or absence on net primary production (NPP) as well as the partitioning between the aboveground and belowground components, in this case, the fraction of total net primary production occurring belowground (fBNPP). I used a factorial experiment to investigate the effects of both precipitation and nematode presence on the components of NPP. I used rainout shelters and an irrigation system to alter precipitation totals, while I used defaunated and re-inoculated soil for the nematode treatments. Precipitation treatment and seasonal soil moisture had no effect on the BNPP and a nonsignificant positive effect on the ANPP. The fBNPP decreased with increasing precipitation and seasonal soil moisture, though without a significant effect. No predator nematodes were found in any of the microcosms at the end of the experiment, though other functional groups of nematodes, including herbivores, were found in the microcosms. Total nematode numbers did not vary significantly between nematode treatments, indicating that the inoculation process did not last for the whole experiment or that nematodes had little plant material to eat and resulted in low population density. Nematode presence did not affect the BNPP, ANPP, or the fBNPP. There were no significant interactions between precipitation and nematode treatment. The results are inconclusive, possibly as a result of ecosystem trends during an unusually high precipitation year, as well as the very low NPP values in the experiment that correlated with low nematode community numbers.
ContributorsWiedenfeld, Amy (Author) / Sala, Osvaldo (Thesis advisor) / Gerber, Leah (Committee member) / Hall, Sharon (Committee member) / Arizona State University (Publisher)
Created2018
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
Vector control plays an important role in the prevention and control of mosquito-borne diseases (MBDs). As there are no (prophylactic) drugs and/or vaccines available for many arboviral diseases (such as zika, chikungunya, Saint Louis encephalitis, Ross River virus), the frontline approach to prevent or reduce disease morbidity and mortality is through the reduction of the mosquito vector population size and/or reducing vector-human contact using insecticides. Frontline tools in malaria (an MBD caused by a parasite) control and elimination have been drugs (targeting the malaria parasite) and insecticides (targeting the vectors) through indoor residual spraying (IRS) (spraying the internal walls and sometimes the roofs of dwellings with residual insecticides to kill adult mosquito vectors), and long-lasting insecticidal nets (LLINs), while arboviral vectors are frequently targeted using outdoor fogging and space spraying (indoor or outdoor spraying of insecticides to kill adult mosquito vectors). Integrative and novel vector control efforts are urgently needed since the aforementioned tools may not be as effective against those mosquito species that are resistant to insecticides and/or have a different (or changed) behavior allowing them to avoid existing tools. In Chapters 2 and 3, I investigate mosquito vector surveillance in Arizona by (i) discussing the species composition and public health implications of the State’s mosquito fauna, and (ii) comparing the effectiveness of 4 different carbon dioxide (CO2) sources in attracting different mosquito species on the Arizona State University Tempe Campus. In Chapters 4 and 5, I investigate a novel vector control tool by (i) completing a literature review on using electric fields (EFs) to control insects, and (ii) presenting novel data on using Insulated Conductor Wires (ICWs) to generate EFs that prevent host-seeking female Aedes aegypti from entering spaces. In Chapter 6, I discuss the non-target effects of chemical malaria control on other arthropods, including other biological and mechanical infectious disease vectors. Overall, this dissertation highlights the important role that the development of novel surveillance and vector control tools could play in improved mosquito control, which ultimately will reduce disease morbidity and mortality.
ContributorsJobe, Ndey Bassin (Author) / Paaijmans, Krijn (Thesis advisor) / Cease, Arianne (Committee member) / Hall, Sharon (Committee member) / Huijben, Silvie (Committee member) / Arizona State University (Publisher)
Created2024
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
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
Description
Decay of plant litter represents an enormous pathway for carbon (C) into the atmosphere but our understanding of the mechanisms driving this process is particularly limited in drylands. While microbes are a dominant driver of litter decay in most ecosystems, their significance in drylands is not well understood and abiotic drivers such as photodegradation are commonly perceived to be more important. I assessed the significance of microbes to the decay of plant litter in the Sonoran Desert. I found that the variation in decay among 16 leaf litter types was correlated with microbial respiration rates (i.e. CO2 emission) from litter, and rates were strongly correlated with water-vapor sorption rates of litter. Water-vapor sorption during high-humidity periods activates microbes and subsequent respiration appears to be a significant decay mechanism. I also found that exposure to sunlight accelerated litter decay (i.e. photodegradation) and enhanced subsequent respiration rates of litter. The abundance of bacteria (but not fungi) on the surface of litter exposed to sunlight was strongly correlated with respiration rates, as well as litter decay, implying that exposure to sunlight facilitated activity of surface bacteria which were responsible for faster decay. I also assessed the response of respiration to temperature and moisture content (MC) of litter, as well as the relationship between relative humidity and MC. There was a peak in respiration rates between 35-40oC, and, unexpectedly, rates increased from 55 to 70oC with the highest peak at 70oC, suggesting the presence of thermophilic microbes or heat-tolerant enzymes. Respiration rates increased exponentially with MC, and MC was strongly correlated with relative humidity. I used these relationships, along with litter microclimate and C loss data to estimate the contribution of this pathway to litter C loss over 34 months. Respiration was responsible for 24% of the total C lost from litter – this represents a substantial pathway for C loss, over twice as large as the combination of thermal and photochemical abiotic emission. My findings elucidate two mechanisms that explain why microbial drivers were more significant than commonly assumed: activation of microbes via water-vapor sorption and high respiration rates at high temperatures.
ContributorsTomes, Alexander (Author) / Day, Thomas (Thesis advisor) / Garcia-Pichel, Ferran (Committee member) / Ball, Becky (Committee member) / Hall, Sharon (Committee member) / Roberson, Robert (Committee member) / Arizona State University (Publisher)
Created2020