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 - 10 of 13
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- All Subjects: Biology
- Creators: Collins, James
- Creators: LaBaer, Joshua
Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.
The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.
This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
Description
Over the past two decades there has been much discussion surrounding the potential of zoos as conservation institutions. Although zoos have clearly intensified their rhetorical and programmatic commitment to conservation (both ex situ and in situ), many critics remain skeptical of these efforts. This study was comprised of two parts: 1) an investigation of the general relationship between U.S. zoological institutions and the conservation agenda, and 2) a more specific single case study of conservation engagement and institutional identity at the Phoenix Zoo. Methods included extensive literature review, expert interviews with scholars and zoo professionals, site visits to the Phoenix Zoo and archival research. I found that the Phoenix Zoo is in the process of consciously creating a conservation-centered institutional identity by implementing and publicizing various conservation initiatives. Despite criticism of the embrace of conservation by zoos today, these institutions will be increasingly important agents of biodiversity protection and conservation education in this century.
ContributorsLove, Karen (Author) / Minteer, Ben (Thesis advisor) / Kinzig, Ann (Committee member) / Collins, James (Committee member) / Arizona State University (Publisher)
Created2014
Description
Evolution is the foundation of biology, yet it remains controversial even among college biology students. Acceptance of evolution is important for students if we want them to incorporate evolution into their scientific thinking. However, students’ religious beliefs are a consistent barrier to their acceptance of evolution due to a perceived conflict between religion and evolution. Using pre-post instructional surveys of students in introductory college biology, Study 1 establishes instructional strategies that can be effective for reducing students' perceived conflict between religion and evolution. Through interviews and qualitative analyses, Study 2 documents how instructors teaching evolution at public universities may be resistant towards implementing strategies that can reduce students' perceived conflict, perhaps because of their own lack of religious beliefs and lack of training and awareness about students' conflict with evolution. Interviews with religious students in Study 3 reveals that religious college biology students can perceive their instructors as unfriendly towards religion which can negatively impact these students' perceived conflict between religion and evolution. Study 4 explores how instructors at Christian universities, who share the same Christian backgrounds as their students, do not struggle with implementing strategies that reduce students' perceived conflict between religion and evolution. Cumulatively, these studies reveal a need for a new instructional framework for evolution education that takes into account the religious cultural difference between instructors who are teaching evolution and students who are learning evolution. As such, a new instructional framework is then described, Religious Cultural Competence in Evolution Education (ReCCEE), that can help instructors teach evolution in a way that can reduce students' perceived conflict between religion and evolution, increase student acceptance of evolution, and create more inclusive college biology classrooms for religious students.
ContributorsBarnes, Maryann Elizabeth (Author) / Brownell, Sara (Thesis advisor) / Nesse, Randolph (Committee member) / Collins, James (Committee member) / Husman, Jenefer (Committee member) / Maienschein, Jane (Committee member) / Arizona State University (Publisher)
Created2018
Description
Guided by Tinto’s Theory of College Student Departure, I conducted a set of five studies to identify factors that influence students’ social integration in college science active learning classes. These studies were conducted in large-enrollment college science courses and some were specifically conducted in undergraduate active learning biology courses. Using qualitative and quantitative methodologies, I identified how students’ identities, such as their gender and LGBTQIA identity, and students’ perceptions of their own intelligence influence their experience in active learning science classes and consequently their social integration in college. I also determined factors of active learning classrooms and instructor behaviors that can affect whether students experience positive or negative social integration in the context of active learning. I found that students’ hidden identities, such as the LGBTQIA identity, are more relevant in active learning classes where students work together and that the increased relevance of one’s identity can have a positive and negative impact on their social integration. I also found that students’ identities can predict their academic self-concept, or their perception of their intelligence as it compares to others’ intelligence in biology, which in turn predicts their participation in small group-discussion. While many students express a fear of negative evaluation, or dread being evaluated negatively by others when speaking out in active learning classes, I identified that how instructors structure group work can cause students to feel more or less integrated into the college science classroom. Lastly, I identified tools that instructors can use, such as name tents and humor, which can positive affect students’ social integration into the college science classroom. In sum, I highlight inequities in students’ experiences in active learning science classrooms and the mechanisms that underlie some of these inequities. I hope this work can be used to create more inclusive undergraduate active learning science courses.
ContributorsCooper, Katelyn M (Author) / Brownell, Sara E (Thesis advisor) / Stout, Valerie (Committee member) / Collins, James (Committee member) / Orchinik, Miles (Committee member) / Zheng, Yi (Committee member) / Arizona State University (Publisher)
Created2018
Description
The complex life cycle and widespread range of infection of Plasmodium parasites, the causal agent of malaria in humans, makes them the perfect organism for the study of various evolutionary mechanisms. In particular, multigene families are considered one of the main sources for genome adaptability and innovation. Within Plasmodium, numerous species- and clade-specific multigene families have major functions in the development and maintenance of infection. Nonetheless, while the evolutionary mechanisms predominant on many species- and clade-specific multigene families have been previously studied, there are far less studies dedicated to analyzing genus common multigene families (GCMFs). I studied the patterns of natural selection and recombination in 90 GCMFs with diverse numbers of gene gain/loss events. I found that the majority of GCMFs are formed by duplications events that predate speciation of mammal Plasmodium species, with many paralogs being neutrally maintained thereafter. In general, multigene families involved in immune evasion and host cell invasion commonly showed signs of positive selection and species-specific gain/loss events; particularly, on Plasmodium species is the simian and rodent clades. A particular multigene family: the merozoite surface protein-7 (msp7) family, is found in all Plasmodium species and has functions related to the erythrocyte invasion. Within Plasmodium vivax, differences in the number of paralogs in this multigene family has been previously explained, at least in part, as potential adaptations to the human host. To investigate this I studied msp7 orthologs in closely related non-human primate parasites where homology was evident. I also estimated paralogs’ evolutionary history and genetic polymorphism. The emerging patterns where compared with those of Plasmodium falciparum. I found that the evolution of the msp7 multigene family is consistent with a Birth-and-Death model where duplications, pseudogenization and gene lost events are common. In order to study additional aspects in the evolution of Plasmodium, I evaluated the trends of long term and short term evolution and the putative effects of vertebrate- host’s immune pressure of gametocytes across various Plasmodium species. Gametocytes, represent the only sexual stage within the Plasmodium life cycle, and are also the transition stages from the vertebrate to the mosquito vector. I found that, while male and female gametocytes showed different levels of immunogenicity, signs of positive selection were not entirely related to the location and presence of immune epitope regions. Overall, these studies further highlight the complex evolutionary patterns observed in Plasmodium.
ContributorsCastillo Siri, Andreina I (Author) / Rosenberg, Michael (Thesis advisor) / Escalante, Ananias (Committee member) / Taylor, Jesse (Committee member) / Collins, James (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
Evolution is a key feature of undergraduate biology education: the AmericanAssociation for the Advancement of Science (AAAS) has identified evolution as one of
the five core concepts of biology, and it is relevant to a wide array of biology-related
careers. If biology instructors want students to use evolution to address scientific
challenges post-graduation, students need to be able to apply evolutionary principles to
real-life situations, and accept that the theory of evolution is the best scientific
explanation for the unity and diversity of life on Earth. In order to help students progress
on both fronts, biology education researchers need surveys that measure evolution
acceptance and assessments that measure students’ ability to apply evolutionary concepts.
This dissertation improves the measurement of student understanding and acceptance of
evolution by (1) developing a novel Evolutionary Medicine Assessment that measures
students’ ability to apply the core principles of Evolutionary Medicine to a variety of
health-related scenarios, (2) reevaluating existing measures of student evolution
acceptance by using student interviews to assess response process validity, and (3)
correcting the validity issues identified on the most widely-used measure of evolution
acceptance - the Measure of Acceptance of the Theory of Evolution (MATE) - by
developing and validating a revised version of this survey: the MATE 2.0.
ContributorsMisheva, Anastasia Taya (Author) / Brownell, Sara (Thesis advisor) / Barnes, Elizabeth (Committee member) / Collins, James (Committee member) / Cooper, Katelyn (Committee member) / Sterner, Beckett (Committee member) / Arizona State University (Publisher)
Created2023
Description
Insecticide resistance is a continuing issue that negatively affects both public health and agriculture and allows vector-borne diseases to spread throughout the globe. To improve resistance management strategies (RMS), robust susceptibility bioassays need to be performed in order to fill the gap of the relationship between resistant and susceptible genotype and phenotype, and a deeper knowledge of how bioassay data relates to vector control success or failure is imperative. A bioassay method that is infrequently used but yields robust results is the topical application bioassay, where the insect is directly treated with a constant volume and concentration of an insecticide via a syringe. To bring more attention to this method, my colleagues and I published a paper in the Journal of Visualized Experiments where the optimized protocol of the topical application bioassay for mosquitoes and fruit flies is described, and the strengths and limitations to the method are explained. To further investigate insecticide susceptibility tests, I set up my individual project where I used Aedes aegypti mosquitoes to compare the topical application bioassay to the commonly used Centers for Disease Control and Prevention (CDC) bottle bioassay and World Health Organization (WHO) tube test. The objective of this study was to test which method exhibited the most variability in mortality results, which would guide the choice of assay to determine the link between resistant and susceptible genotype and phenotype. The results showed that the topical application method did indeed exhibit the least amount of variation, followed by the CDC bottle bioassay (WHO data is currently being collected). This suggests that the topical application bioassay could be a useful tool in insecticide resistance surveillance studies, and, depending on the goal, may be better than the CDC and WHO tube tests for assessing resistance levels at a given site. This study challenges the value of the widely used CDC and WHO assays and provides a discussion on the importance of technical and practical resistance assays. This will help vector control specialists to collect accurate surveillance data that will inform effective RMS.
ContributorsAlthoff, Rachel (Author) / Huijben, Silvie (Thesis advisor) / Harris, Robin (Committee member) / Collins, James (Committee member) / Arizona State University (Publisher)
Created2022
Description
Emerging pathogens present several challenges to medical diagnostics. Primarily, the exponential spread of a novel pathogen through naïve populations require a rapid and overwhelming diagnostic response at the site of outbreak. While point-of-care (PoC) platforms have been developed for detection of antigens, serologic responses, and pathogenic genomes, only nucleic acid diagnostics currently have the potential to be developed and manufactured within weeks of an outbreak owing to the speed of next-generation sequencing and custom DNA synthesis. Among nucleic acid diagnostics, isothermal amplification strategies are uniquely suited for PoC implementation due to their simple instrumentation and lack of thermocycling requirement. Unfortunately, isothermal strategies are currently prone to spurious nonspecific amplification, hindering their specificity and necessitating extensive empirical design pipelines that are both time and resource intensive. In this work, isothermal amplification strategies are extensively compared for their feasibility of implementation in outbreak response scenarios. One such technology, Loop-mediated Amplification (LAMP), is identified as having high-potential for rapid development and PoC deployment. Various approaches to abrogating nonspecific amplification are described including a novel in silico design tool based on coarse-grained simulation of interactions between thermophilic DNA polymerase and DNA strands in isothermal reaction conditions. Nonspecific amplification is shown to be due to stabilization of primer secondary structures by high concentrations of Bst DNA polymerase and a mechanism of micro-complement-mediated cross-priming is demonstrated as causal via nanopore sequencing of nonspecific reaction products. The resulting computational model predicts primer set background in 64% of 67 test assays and its usefulness is illustrated further by determining problematic primers in a West Nile Virus-specific LAMP primer set and optimizing primer 3’ nucleotides to eliminate micro-complements within the reaction, resulting in inhibition of background accumulation. Finally, the emergence of Orthopox monkeypox (MPXV) as a recurring threat is discussed and SimCycle is utilized to develop a novel technique for clade-specific discrimination of MPXV based on bridging viral genomic rearrangements (Bridging LAMP). Bridging LAMP is implemented in a 4-plex microfluidic format and demonstrates 100% sensitivity in detection of 100 copies of viral lysates and 45 crude MPXV-positive patient samples collected during the 2022 Clade IIb outbreak.
ContributorsKnappenberger, Mark Daniel (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Committee member) / Roberson, Robert (Committee member) / Lindsay, Stuart (Committee member) / Arizona State University (Publisher)
Created2023
Description
According to the World Health Organization, cancer is one of the leading causes of death around the world. Although early diagnostics using biomarkers and improved treatments with targeted therapy have reduced the rate of cancer related mortalities, there remain many unknowns regarding the contributions of the tumor microenvironment to cancer progression and therapeutic resistance. The tumor microenvironment plays a significant role by manipulating the progression of cancer cells through biochemical and biophysical signals from the surrounding stromal cells along with the extracellular matrix. As such, there is a critical need to understand how the tumor microenvironment influences the molecular mechanisms underlying cancer metastasis to facilitate the discovery of better therapies. This thesis described the development of microfluidic technologies to study the interplay of cancer cells with their surrounding microenvironment. The microfluidic model was used to assess how exposure to chemoattractant, epidermal growth factor (EGF), impacted 3D breast cancer cell invasion and enhanced cell motility speed was noted in the presence of EGF validating physiological cell behavior. Additionally, breast cancer and patient-derived cancer-associated fibroblast (CAF) cells were co-cultured to study cell-cell crosstalk and how it affected cancer invasion. GPNMB was identified as a novel gene of interest and it was shown that CAFs enhanced breast cancer invasion by up-regulating the expression of GPNMB on breast cancer cells resulting in increased migration speed. Lastly, this thesis described the design, biological validation, and use of this microfluidic platform as a new in vitro 3D organotypic model to study mechanisms of glioma stem cell (GSC) invasion in the context of a vascular niche. It was confirmed that CXCL12-CXCR4 signaling is involved in promoting GSC invasion in a 3D vascular microenvironment, while also demonstrating the effectiveness of the microfluidic as a drug screening assay. Taken together, the broader impacts of the microfluidic model developed in this dissertation include, a possible alternative platform to animal testing that is focused on mimicking human physiology, a potential ex vivo platform using patient-derived cells for studying the interplay of cancer cells with its surrounding microenvironment, and development of future therapeutic strategies tailored toward disrupting key molecular pathways involved in regulatory mechanisms of cancer invasion.
ContributorsTruong, Danh, Ph.D (Author) / Nikkhah, Mehdi (Thesis advisor) / LaBaer, Joshua (Committee member) / Smith, Barbara (Committee member) / Mouneimne, Ghassan (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2018