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: Perrings, Charles
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
This dissertation consists of three substantive chapters. The first substantive chapter investigates the premature harvesting problem in fisheries. Traditionally, yield-per-recruit analysis has been used to both assess and address the premature harvesting of fish stocks. However, the fact that fish size often affects the unit price suggests that this approach may be inadequate. In this chapter, I first synthesize the conventional yield-per-recruit analysis, and then extend this conventional approach by incorporating a size-price function for a revenue-per-recruit analysis. An optimal control approach is then used to derive a general bioeconomic solution for the optimal harvesting of a short-lived single cohort. This approach prevents economically premature harvesting and provides an "optimal economic yield". By comparing the yield- and revenue-per-recruit management strategies with the bioeconomic management strategy, I am able to test the economic efficiency of the conventional yield-per-recruit approach. This is illustrated with a numerical study. It shows that a bioeconomic strategy can significantly improve economic welfare compared with the yield-per-recruit strategy, particularly in the face of high natural mortality. Nevertheless, I find that harvesting on a revenue-per-recruit basis improves management policy and can generate a rent that is close to that from bioeconomic analysis, in particular when the natural mortality is relatively low.
The second substantive chapter explores the conservation potential of a whale permit market under bounded economic uncertainty. Pro- and anti-whaling stakeholders are concerned about a recently proposed, "cap and trade" system for managing the global harvest of whales. Supporters argue that such an approach represents a novel solution to the current gridlock in international whale management. In addition to ethical objections, opponents worry that uncertainty about demand for whale-based products and the environmental benefits of conservation may make it difficult to predict the outcome of a whale share market. In this study, I use population and economic data for minke whales to examine the potential ecological consequences of the establishment of a whale permit market in Norway under bounded but significant economic uncertainty. A bioeconomic model is developed to evaluate the influence of economic uncertainties associated with pro- and anti- whaling demands on long-run steady state whale population size, harvest, and potential allocation. The results indicate that these economic uncertainties, in particular on the conservation demand side, play an important role in determining the steady state ecological outcome of a whale share market. A key finding is that while a whale share market has the potential to yield a wide range of allocations between conservation and whaling interests - outcomes in which conservationists effectively "buy out" the whaling industry seem most likely.
The third substantive chapter examines the sea lice externality between farmed fisheries and wild fisheries. A central issue in the debate over the effect of fish farming on the wild fisheries is the nature of sea lice population dynamics and the wild juvenile mortality rate induced by sea lice infection. This study develops a bioeconomic model that integrates sea lice population dynamics, fish population dynamics, aquaculture and wild capture salmon fisheries in an optimal control framework. It provides a tool to investigate sea lice control policy from the standpoint both of private aquaculture producers and wild fishery managers by considering the sea lice infection externality between farmed and wild fisheries. Numerical results suggest that the state trajectory paths may be quite different under different management regimes, but approach the same steady state. Although the difference in economic benefits is not significant in the particular case considered due to the low value of the wild fishery, I investigate the possibility of levying a tax on aquaculture production for correcting the sea lice externality generated by fish farms.
The second substantive chapter explores the conservation potential of a whale permit market under bounded economic uncertainty. Pro- and anti-whaling stakeholders are concerned about a recently proposed, "cap and trade" system for managing the global harvest of whales. Supporters argue that such an approach represents a novel solution to the current gridlock in international whale management. In addition to ethical objections, opponents worry that uncertainty about demand for whale-based products and the environmental benefits of conservation may make it difficult to predict the outcome of a whale share market. In this study, I use population and economic data for minke whales to examine the potential ecological consequences of the establishment of a whale permit market in Norway under bounded but significant economic uncertainty. A bioeconomic model is developed to evaluate the influence of economic uncertainties associated with pro- and anti- whaling demands on long-run steady state whale population size, harvest, and potential allocation. The results indicate that these economic uncertainties, in particular on the conservation demand side, play an important role in determining the steady state ecological outcome of a whale share market. A key finding is that while a whale share market has the potential to yield a wide range of allocations between conservation and whaling interests - outcomes in which conservationists effectively "buy out" the whaling industry seem most likely.
The third substantive chapter examines the sea lice externality between farmed fisheries and wild fisheries. A central issue in the debate over the effect of fish farming on the wild fisheries is the nature of sea lice population dynamics and the wild juvenile mortality rate induced by sea lice infection. This study develops a bioeconomic model that integrates sea lice population dynamics, fish population dynamics, aquaculture and wild capture salmon fisheries in an optimal control framework. It provides a tool to investigate sea lice control policy from the standpoint both of private aquaculture producers and wild fishery managers by considering the sea lice infection externality between farmed and wild fisheries. Numerical results suggest that the state trajectory paths may be quite different under different management regimes, but approach the same steady state. Although the difference in economic benefits is not significant in the particular case considered due to the low value of the wild fishery, I investigate the possibility of levying a tax on aquaculture production for correcting the sea lice externality generated by fish farms.
ContributorsHuang, Biao (Author) / Abbott, Joshua K (Thesis advisor) / Perrings, Charles (Thesis advisor) / Gerber, Leah R. (Committee member) / Muneepeerakul, Rachata (Committee member) / Schoon, Michael (Committee member) / Arizona State University (Publisher)
Created2014
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
The spread of dengue worldwide currently places half of the world’s population at risk. In the absence of a dengue vaccine, control of the disease requires control of the mosquito species that transmit the virus. The most important of these is. Advances in research detailing the responsiveness of Aedes aegypti to small changes in climate enable the production of more sophisticated remote sensing and surveillance techniques for monitoring these populations. Close monitoring of global dengue activity and outbreaks likewise enables a greater specificity when determining to which human populations the virus is most likely to spread. There have been no locally acquired cases in Arizona to date, but the high abundance of Aedes aegypti in the Phoenix Metropolitan area raises concern within the Arizona Department of Health Services over the potential transmission of dengue in the city. This study develops a model that combines mosquito abundance, micro-climatic and demographic information to delineate regions in Phoenix that are most support transmission of dengue. The first chapter focuses on the impact that daytime high and low temperatures have on Aedes aegypti’s ability to become infectious with dengue. It argues that NDVI (normal difference vegetative index) imaging of the Phoenix area can be used to plot areas where mosquitoes are most likely to become competent vectors. The second chapter focuses on the areas in the city where mosquitoes are most likely to be exposed to the virus. Based on proximity to Phoenix and the high volume of traffic across the Arizona-Mexico border, I treat the Mexican state of Sonora as the source of infection. I combine these two analyses, micro-climatic and demographic, to produce maps of Phoenix that show the locations with the highest likelihood of transmission overall.
ContributorsHughes, Tyler (Author) / Perrings, Charles (Thesis advisor) / Kinzig, Ann (Committee member) / Hall, Sharon J (Committee member) / Arizona State University (Publisher)
Created2016
Description
The closer integration of the world economy has yielded many positive benefits including the worldwide diffusion of innovative technologies and efficiency gains following the widening of international markets. However, closer integration also has negative consequences. Specifically, I focus on the ecology and economics of the spread of species and pathogens. I approach the problem using theoretical and applied models in ecology and economics. First, I use a multi-species theoretical network model to evaluate the ability of dispersal to maintain system-level biodiversity and productivity. I then extend this analysis to consider the effects of dispersal in a coupled social-ecological system where people derive benefits from species. Finally, I estimate an empirical model of the foot and mouth disease risks of trade. By combining outbreak and trade data I estimate the disease risks associated with the international trade in live animals while controlling for the biosecurity measures in place in importing countries and the presence of wild reservoirs. I find that the risks associated with the spread and dispersal of species may be positive or negative, but that this relationship depends on the ecological and economic components of the system and the interactions between them.
ContributorsShanafelt, David William (Author) / Perrings, Charles (Thesis advisor) / Fenichel, Eli (Committee member) / Richards, Timorthy (Committee member) / Janssen, Marco (Committee member) / Collins, James (Committee member) / Arizona State University (Publisher)
Created2016
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