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.
Displaying 1 - 8 of 8
Filtering by
- All Subjects: Biology
- Creators: Angilletta, Michael
- Creators: Stafford, Phillip
Description
The advent of new high throughput technology allows for increasingly detailed characterization of the immune system in healthy, disease, and age states. The immune system is composed of two main branches: the innate and adaptive immune system, though the border between these two states is appearing less distinct. The adaptive immune system is further split into two main categories: humoral and cellular immunity. The humoral immune response produces antibodies against specific targets, and these antibodies can be used to learn about disease and normal states. In this document, I use antibodies to characterize the immune system in two ways: 1. I determine the Antibody Status (AbStat) from the data collected from applying sera to an array of non-natural sequence peptides, and demonstrate that this AbStat measure can distinguish between disease, normal, and aged samples as well as produce a single AbStat number for each sample; 2. I search for antigens for use in a cancer vaccine, and this search results in several candidates as well as a new hypothesis. Antibodies provide us with a powerful tool for characterizing the immune system, and this natural tool combined with emerging technologies allows us to learn more about healthy and disease states.
ContributorsWhittemore, Kurt (Author) / Sykes, Kathryn (Thesis advisor) / Johnston, Stephen A. (Committee member) / Jacobs, Bertram (Committee member) / Stafford, Phillip (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2014
Description
The healthcare system in this country is currently unacceptable. New technologies may contribute to reducing cost and improving outcomes. Early diagnosis and treatment represents the least risky option for addressing this issue. Such a technology needs to be inexpensive, highly sensitive, highly specific, and amenable to adoption in a clinic. This thesis explores an immunodiagnostic technology based on highly scalable, non-natural sequence peptide microarrays designed to profile the humoral immune response and address the healthcare problem. The primary aim of this thesis is to explore the ability of these arrays to map continuous (linear) epitopes. I discovered that using a technique termed subsequence analysis where epitopes could be decisively mapped to an eliciting protein with high success rate. This led to the discovery of novel linear epitopes from Plasmodium falciparum (Malaria) and Treponema palladium (Syphilis), as well as validation of previously discovered epitopes in Dengue and monoclonal antibodies. Next, I developed and tested a classification scheme based on Support Vector Machines for development of a Dengue Fever diagnostic, achieving higher sensitivity and specificity than current FDA approved techniques. The software underlying this method is available for download under the BSD license. Following this, I developed a kinetic model for immunosignatures and tested it against existing data driven by previously unexplained phenomena. This model provides a framework and informs ways to optimize the platform for maximum stability and efficiency. I also explored the role of sequence composition in explaining an immunosignature binding profile, determining a strong role for charged residues that seems to have some predictive ability for disease. Finally, I developed a database, software and indexing strategy based on Apache Lucene for searching motif patterns (regular expressions) in large biological databases. These projects as a whole have advanced knowledge of how to approach high throughput immunodiagnostics and provide an example of how technology can be fused with biology in order to affect scientific and health outcomes.
ContributorsRicher, Joshua Amos (Author) / Johnston, Stephen A. (Thesis advisor) / Woodbury, Neal (Committee member) / Stafford, Phillip (Committee member) / Papandreou-Suppappola, Antonia (Committee member) / Arizona State University (Publisher)
Created2014
Description
African Swine Fever (ASF), endemic in many African countries, is now spreading to other continents. Though ASF is capable of incurring serious economic losses in affected countries, no vaccine exists to provide immunity to animals. Disease control relies largely on rapid diagnosis and the implementation of movement restrictions and strict eradication programs. Developing a scalable, accurate and low cost diagnostic for ASF will be of great help for the current situation. CIM's 10K random peptide microarray is a new high-throughput platform that allows systematic investigations of immune responses associated with disease and shows promise as a diagnostic tool. In this study, this new technology was applied to characterize the immune responses of ASF virus (ASFV) infections and immunizations. Six sets of sera from ASFV antigen immunized pigs, 6 sera from infected pigs and 20 sera samples from unexposed pigs were tested and analyzed statistically. Results show that both ASFV antigen immunized pigs and ASFV viral infected pigs can be distinguished from unexposed pigs. Since it appears that immune responses to other viral infections are also distinguishable on this platform, it holds the potential of being useful in developing a new ASF diagnostic. The ability of this platform to identify specific ASFV antibody epitopes was also explored. A subtle motif was found to be shared among a set of peptides displaying the highest reactivity for an antigen specific antibody. However, this motif does not seem to match with any antibody epitopes predicted by a linear antibody epitope prediction.
ContributorsXiao, Liang (Author) / Sykes, Kathryn (Thesis advisor) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Immunotherapy has been revitalized with the advent of immune checkpoint blockade
treatments, and neo-antigens are the targets of immune system in cancer patients who
respond to the treatments. The cancer vaccine field is focused on using neo-antigens from
unique point mutations of genomic sequence in the cancer patient for making
personalized cancer vaccines. However, we choose a different path to find frameshift
neo-antigens at the mRNA level and develop broadly effective cancer vaccines based on
frameshift antigens.
In this dissertation, I have summarized and characterized all the potential frameshift
antigens from microsatellite regions in human, dog and mouse. A list of frameshift
antigens was validated by PCR in tumor samples and the mutation rate was calculated for
one candidate – SEC62. I develop a method to screen the antibody response against
frameshift antigens in human and dog cancer patients by using frameshift peptide arrays.
Frameshift antigens selected by positive antibody response in cancer patients or by MHC
predictions show protection in different mouse tumor models. A dog version of the
cancer vaccine based on frameshift antigens was developed and tested in a small safety
trial. The results demonstrate that the vaccine is safe and it can induce strong B and T cell
immune responses. Further, I built the human exon junction frameshift database which
includes all possible frameshift antigens from mis-splicing events in exon junctions, and I
develop a method to find potential frameshift antigens from large cancer
immunosignature dataset with these databases. In addition, I test the idea of ‘early cancer
diagnosis, early treatment’ in a transgenic mouse cancer model. The results show that
ii
early treatment gives significantly better protection than late treatment and the correct
time point for treatment is crucial to give the best clinical benefit. A model for early
treatment is developed with these results.
Frameshift neo-antigens from microsatellite regions and mis-splicing events are
abundant at mRNA level and they are better antigens than neo-antigens from point
mutations in the genomic sequences of cancer patients in terms of high immunogenicity,
low probability to cause autoimmune diseases and low cost to develop a broadly effective
vaccine. This dissertation demonstrates the feasibility of using frameshift antigens for
cancer vaccine development.
treatments, and neo-antigens are the targets of immune system in cancer patients who
respond to the treatments. The cancer vaccine field is focused on using neo-antigens from
unique point mutations of genomic sequence in the cancer patient for making
personalized cancer vaccines. However, we choose a different path to find frameshift
neo-antigens at the mRNA level and develop broadly effective cancer vaccines based on
frameshift antigens.
In this dissertation, I have summarized and characterized all the potential frameshift
antigens from microsatellite regions in human, dog and mouse. A list of frameshift
antigens was validated by PCR in tumor samples and the mutation rate was calculated for
one candidate – SEC62. I develop a method to screen the antibody response against
frameshift antigens in human and dog cancer patients by using frameshift peptide arrays.
Frameshift antigens selected by positive antibody response in cancer patients or by MHC
predictions show protection in different mouse tumor models. A dog version of the
cancer vaccine based on frameshift antigens was developed and tested in a small safety
trial. The results demonstrate that the vaccine is safe and it can induce strong B and T cell
immune responses. Further, I built the human exon junction frameshift database which
includes all possible frameshift antigens from mis-splicing events in exon junctions, and I
develop a method to find potential frameshift antigens from large cancer
immunosignature dataset with these databases. In addition, I test the idea of ‘early cancer
diagnosis, early treatment’ in a transgenic mouse cancer model. The results show that
ii
early treatment gives significantly better protection than late treatment and the correct
time point for treatment is crucial to give the best clinical benefit. A model for early
treatment is developed with these results.
Frameshift neo-antigens from microsatellite regions and mis-splicing events are
abundant at mRNA level and they are better antigens than neo-antigens from point
mutations in the genomic sequences of cancer patients in terms of high immunogenicity,
low probability to cause autoimmune diseases and low cost to develop a broadly effective
vaccine. This dissertation demonstrates the feasibility of using frameshift antigens for
cancer vaccine development.
ContributorsZhang, Jian (Author) / Johnston, Stephen Albert (Thesis advisor) / Chang, Yung (Committee member) / Stafford, Phillip (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2018
Description
There is considerable recent interest in the dynamic nature of immune function in the context of an animal’s internal and external environment. An important focus within this field of ecoimmunology is on how availability of resources such as energy can alter immune function. Water is an additional resource that drives animal development, physiology, and behavior, yet the influence hydration has on immunity has received limited attention. In particular, hydration state may have the greatest potential to drive fluctuations in immunity and other physiological functions in species that live in water-limited environments where they may experience periods of dehydration. To shed light on the sensitivity of immune function to hydration state, I first tested the effect of hydration states (hydrated, dehydrated, and rehydrated) and digestive states on innate immunity in the Gila monster, a desert-dwelling lizard. Though dehydration is often thought to be stressful and, if experienced chronically, likely to decrease immune function, dehydration elicited an increase in immune response in this species, while digestive state had no effect. Next, I tested whether dehydration was indeed stressful, and tested a broader range of immune measures. My findings validated the enhanced innate immunity across additional measures and revealed that Gila monsters lacked a significant stress hormone response during dehydration (though results were suggestive). I next sought to test if life history (in terms of environmental stability) drives these differences in dehydration responses using a comparative approach. I compared four confamilial pairs of squamate species that varied in habitat type within each pair—four species that are adapted to xeric environments and four that are adapted to more mesic environments. No effect of life history was detected between groups, but hydration was a driver of some measures of innate immunity and of stress hormone concentrations in multiple species. Additionally, species that exhibited a stress response to dehydration did not have decreased innate immunity, suggesting these physiological responses may often be decoupled. My dissertation work provides new insight into the relationship between hydration, stress, and immunity, and it may inform future work exploring disease transmission or organismal responses to climate change.
ContributorsMoeller, Karla T (Author) / DeNardo, Dale (Thesis advisor) / Angilletta, Michael (Committee member) / French, Susannah (Committee member) / Rutowski, Ronald (Committee member) / Sabo, John (Committee member) / Arizona State University (Publisher)
Created2016
Description
Desert environments provide considerable challenges to organisms because of high temperatures and limited food and water resources. Accordingly, desert species have behavioral and physiological traits that enable them to cope with these constraints. However, continuing human activity as well as anticipated further changes to the climate and the vegetative community pose a great challenge to such balance between an organism and its environment. This is especially true in the Arabian Desert, where climate conditions are extreme and environmental disturbances substantial. This study combined laboratory and field components to enhance our understanding of dhub (Uromastyx aegyptius) ecophysiology and determine whether habitat protection influences dhub behavior and physiology.
Results of this study showed that while body mass and body condition consistently diminished as the active season progressed, they were both greater in protected habitats compared to non-protected habitats, regardless of season. Dhubs surface activity and total body water decreased while evaporative water loss and body temperature increased as the active season progressed and ambient temperature got hotter. Total body water was also significantly affected by habitat protection.
Overall, this study revealed that, while habitat protection provided more vegetation, it had little effect on seasonal changes in surface activity. While resource availability in protected areas might allow for larger dhub populations, unprotected areas showed similar body morphometrics, activity, and body temperatures. By developing an understanding of how different coping strategies are linked to particular ecological, morphological, and phylogenetic traits, we will be able to make more accurate predictions regarding the vulnerability of species. By combining previous studies pertaining to conservation of protected species with the results of my study, a number of steps in ecosystem management are recommended to help in the preservation of dhubs in the Kuwaiti desert.
Results of this study showed that while body mass and body condition consistently diminished as the active season progressed, they were both greater in protected habitats compared to non-protected habitats, regardless of season. Dhubs surface activity and total body water decreased while evaporative water loss and body temperature increased as the active season progressed and ambient temperature got hotter. Total body water was also significantly affected by habitat protection.
Overall, this study revealed that, while habitat protection provided more vegetation, it had little effect on seasonal changes in surface activity. While resource availability in protected areas might allow for larger dhub populations, unprotected areas showed similar body morphometrics, activity, and body temperatures. By developing an understanding of how different coping strategies are linked to particular ecological, morphological, and phylogenetic traits, we will be able to make more accurate predictions regarding the vulnerability of species. By combining previous studies pertaining to conservation of protected species with the results of my study, a number of steps in ecosystem management are recommended to help in the preservation of dhubs in the Kuwaiti desert.
ContributorsAl-Sayegh, Mohammed (Author) / DeNardo, Dale (Thesis advisor) / Angilletta, Michael (Committee member) / Smith, Andrew (Committee member) / Sabo, John (Committee member) / Majeed, Qais (Committee member) / Arizona State University (Publisher)
Created2017
Description
The migratory grasshopper (Melanoplus sanguinipes) is one of the most economically important grasshoppers in the western rangelands of the United States (US), capable of causing incredible amounts of damage to crops and rangelands. While M. sanguinipes has been the focus of many research studies, areas like field nutritional physiology and ecology, and interactions between nutritional physiology and biopesticide resistance have very little research. This dissertation presents a multifaceted approach through three research-driven chapters that examine the nutritional physiology of M. sanguinipes and how it interacts with an entomopathogenic fungus for grasshopper management, as well as the challenges of using biopesticides for grasshopper management. Using the Geometric Framework for Nutrition (GFN), I established baseline macronutrient intake for M. sanguinipes, both in laboratory and field populations. Through this work, I found that field and lab populations can exhibit different protein (p) to carbohydrate (c) ratios, or Intake Targets (ITs), but that the field populations had ITs that matched the nutrients available in their environment. I also used the GFN to show that infections with the fungal entomopathogen Metarhizium robertsii DWR2009 did not alter ITs in M. sanguinipes. Although, when confined to carbohydrate- or protein-biased diets, infected grasshoppers had a slightly extended lifespan relative to grasshoppers fed balanced protein:carbohydrate diets. Interestingly, in a postmortem for the grasshopper, the fungus was only able to effectively sporulate on grasshoppers fed the 1p:1c diets, suggesting that grasshopper diet can have substantial impacts on the spread of fungal biopesticides throughout a population, in the absence of any inhibitory abiotic factors. Lastly, I examined the major barriers to fungal and microsporidian biopesticide usage in the United States, including low efficacy, thermal and environmental sensitivity, non-target effects, unregistered or restricted use, and economic or accessibility barriers. I also explored potential solutions to these challenges. This dissertation's focus on Melanoplus sanguinipes and Metarhizium roberstii Strain DWR2009, generates new information about how nutritional physiology and immunology intersect to impact M. sanguinipes performance. The methodology in each of the experimental chapters provides a framework for examining other problematic grasshopper species, by determining baseline nutritional physiology, and coupling nutrition with immunology to maximize the effectiveness of biological pesticides.
ContributorsZembrzuski, Deanna (Author) / Cease, Arianne (Thesis advisor) / Harrison, Jon (Committee member) / Angilletta, Michael (Committee member) / Jaronski, Stefan (Committee member) / Arizona State University (Publisher)
Created2023
Description
Ectotherms rely on external heat to attain target body temperatures which can vary based on the animal’s current physiological activity. Many ectotherms become thermophilic (“heat-loving”) during crucial physiological processes like digestion and reproduction, behaviorally thermoregulating to increase body temperature higher than what they otherwise prefer. However, there is a positive relationship between body temperature and water loss that dictates increasing body temperature typically elicits an increase in water loss. Animals that inhabit areas where water is at least seasonally limited (e.g., deserts, wet-dry forests) may face a tradeoff between prioritizing behavioral thermophily to optimize physiological processes versus prioritizing water balance and potentially sacrificing some aspect of total performance capability.It is thus far unknown how reduced water availability and subsequent dehydration may influence thermophily in ectotherms. I hypothesized that behaviorally thermoregulating ectotherms exhibit thermophily during critical physiological events, and the extent to which thermophily is expressed is influenced by the animal’s hydric state. Using Children’s pythons (Antaresia childreni), I investigated the effects of dehydration on behavioral thermophily during digestion and reproduction. I found that dehydration caused a suppression in digestion-associated thermophily, where dehydrated snakes returned to pre-feeding body temperature sooner than they did when they were hydrated. In contrast, water deprivation at different reproductive stages had no effect on thermophily despite leading to a significant increase in the female’s plasma osmolality.
ii
Additionally, the timing of water deprivation during reproduction had differing effects on plasma osmolality and circulating triglyceride, total protein, and corticosterone concentrations. My research provides evidence of the sensitive and complex dynamic between body temperature, water balance, and physiological processes. At a time when many dry ecosystems are becoming hotter and drier, my investigation of dehydration and its influence on thermal dynamics and physiological metrics provides insight into cryptic effects on the vital processes of digestion and reproduction.
ContributorsAzzolini, Jill L. (Author) / Denardo, Dale F. (Thesis advisor) / John-Alder, Henry (Committee member) / Angilletta, Michael (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2023