Barrett, The Honors College Thesis/Creative Project Collection
Barrett, The Honors College at Arizona State University proudly showcases the work of undergraduate honors students by sharing this collection exclusively with the ASU community.
Barrett accepts high performing, academically engaged undergraduate students and works with them in collaboration with all of the other academic units at Arizona State University. All Barrett students complete a thesis or creative project which is an opportunity to explore an intellectual interest and produce an original piece of scholarly research. The thesis or creative project is supervised and defended in front of a faculty committee. Students are able to engage with professors who are nationally recognized in their fields and committed to working with honors students. Completing a Barrett thesis or creative project is an opportunity for undergraduate honors students to contribute to the ASU academic community in a meaningful way.
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Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Transient Receptor Potential (TRP) ion channels are a diverse family of nonselective, polymodal sensors in uni- and multicellular eukaryotes that are implicated in an assortment of biological contexts and human disease. The cold-activated TRP Melastatin-8 (TRPM8) channel, also recognized as the human body's primary cold sensor, is among the few TRP channels responsible for thermosensing. Despite sustained interest in the channel, the mechanisms underlying TRPM8 activation, modulation, and gating have proved challenging to study and remain poorly understood. In this thesis, I offer data collected on various expression, extraction, and purification conditions tested in E. Coli expression systems with the aim to optimize the generation of a structurally stable and functional human TRPM8 pore domain (S5 and S6) construct for application in structural biology studies. These studies, including the biophysical technique nuclear magnetic spectroscopy (NMR), among others, will be essential for elucidating the role of the TRPM8 pore domain in in regulating ligand binding, channel gating, ion selectively, and thermal sensitivity. Moreover, in the second half of this thesis, I discuss the ligation-independent megaprimer PCR of whole-plasmids (MEGAWHOP PCR) cloning technique, and how it was used to generate chimeras between TRPM8 and its nearest analog TRPM2. I review steps taken to optimize the efficiency of MEGAWHOP PCR and the implications and unique applications of this novel methodology for advancing recombinant DNA technology. I lastly present preliminary electrophysiological data on the chimeras, employed to isolate and study the functional contributions of each individual transmembrane helix (S1-S6) to TRPM8 menthol activation. These studies show the utility of the TRPM8\u2014TRPM2 chimeras for dissecting function of TRP channels. The average current traces analyzed thus far indicate that the S2 and S3 helices appear to play an important role in TRPM8 menthol modulation because the TRPM8[M2S2] and TRPM8[M2S3] chimeras significantly reduce channel conductance in the presence of menthol. The TRPM8[M2S4] chimera, oppositely, increases channel conductance, implying that the S4 helix in native TRPM8 may suppress menthol modulation. Overall, these findings show that there is promise in the techniques chosen to identify specific regions of TRPM8 crucial to menthol activation, though the methods chosen to study the TRPM8 pore independent from the whole channel may need to be reevaluated. Further experiments will be necessary to refine TRPM8 pore solubilization and purification before structural studies can proceed, and the electrophysiology traces observed for the chimeras will need to be further verified and evaluated for consistency and physiological significance.
ContributorsWaris, Maryam Siddika (Author) / Van Horn, Wade (Thesis director) / Redding, Kevin (Committee member) / School of Molecular Sciences (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Background: Noninvasive MRI methods that can accurately detect subtle brain changes are highly desirable when studying disease-modifying interventions. Texture analysis is a novel imaging technique which utilizes the extraction of a large number of image features with high specificity and predictive power. In this investigation, we use texture analysis to assess and classify age-related changes in the right and left hippocampal regions, the areas known to show some of the earliest change in Alzheimer's disease (AD). Apolipoprotein E (APOE)'s e4 allele confers an increased risk for AD, so studying differences in APOE e4 carriers may help to ascertain subtle brain changes before there has been an obvious change in behavior. We examined texture analysis measures that predict age-related changes, which reflect atrophy in a group of cognitively normal individuals. We hypothesized that the APOE e4 carriers would exhibit significant age-related differences in texture features compared to non-carriers, so that the predictive texture features hold promise for early assessment of AD. Methods: 120 normal adults between the ages of 32 and 90 were recruited for this neuroimaging study from a larger parent study at Mayo Clinic Arizona studying longitudinal cognitive functioning (Caselli et al., 2009). As part of the parent study, the participants were genotyped for APOE genetic polymorphisms and received comprehensive cognitive testing every two years, on average. Neuroimaging was done at Barrow Neurological Institute and a 3D T1-weighted magnetic resonance image was obtained during scanning that allowed for subsequent texture analysis processing. Voxel-based features of the appearance, structure, and arrangement of these regions of interest were extracted utilizing the Mayo Clinic Python Texture Analysis Pipeline (pyTAP). Algorithms applied in feature extraction included Grey-Level Co-Occurrence Matrix (GLCM), Gabor Filter Banks (GFB), Local Binary Patterns (LBP), Discrete Orthogonal Stockwell Transform (DOST), and Laplacian-of-Gaussian Histograms (LoGH). Principal component (PC) analysis was used to reduce the dimensionality of the algorithmically selected features to 13 PCs. A stepwise forward regression model was used to determine the effect of APOE status (APOE e4 carriers vs. noncarriers), and the texture feature principal components on age (as a continuous variable). After identification of 5 significant predictors of age in the model, the individual feature coefficients of those principal components were examined to determine which features contributed most significantly to the prediction of an aging brain. Results: 70 texture features were extracted for the two regions of interest in each participant's scan. The texture features were coded as 70 initial components andwere rotated to generate 13 principal components (PC) that contributed 75% of the variance in the dataset by scree plot analysis. The forward stepwise regression model used in this exploratory study significantly predicted age, accounting for approximately 40% of the variance in the data. The regression model revealed 5 significant regressors (2 right PC's, APOE status, and 2 left PC by APOE interactions). Finally, the specific texture features that contributed to each significant PCs were identified. Conclusion: Analysis of image texture features resulted in a statistical model that was able to detect subtle changes in brain integrity associated with age in a group of participants who are cognitively normal, but have an increased risk of developing AD based on the presence of the APOE e4 phenotype. This is an important finding, given that detecting subtle changes in regions vulnerable to the effects of AD in patients could allow certain texture features to serve as noninvasive, sensitive biomarkers predictive of AD. Even with only a small number of patients, the ability for us to determine sensitive imaging biomarkers could facilitate great improvement in speed of detection and effectiveness of AD interventions..
ContributorsSilva, Annelise Michelle (Author) / Baxter, Leslie (Thesis director) / McBeath, Michael (Committee member) / Presson, Clark (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
A series of mitochondria targeting probes was synthesized for the purpose of exploring the feasibility of a mitochondria targeting fluorescent sensor. Of the probes, the probe with a two carbon spacer showed the best co-localization from staining with the established MitoTracker Red® FM, indicating a potential development of the probe into mitochondria targeting sensor. However, cytotoxicity was observed for the probe with a six carbon spacer. Three additional mitochondria targeting fluorescent probes of longer spacer groups were synthesized, but the cytotoxicity was not observed to be as high as that of the probe with a two carbon spacer. The cytotoxicity was characterized to be that of caspase dependent cell death. To screen for a possible effect on apoptosis due to the mitochondrial probe, three fluorescent fusion proteins binding the anti-apoptotic proteins were designed and expressed. Each purified fusion protein was then incubated with the cytotoxic mitochondrial probe, and the mixture was isolated by running an affinity column. The fluorescence analysis of eluted fractions showed preliminary data of possible interaction between the protein and the mitochondrial probe.
ContributorsLee, Fred (Author) / Meldrum, Deirdre R. (Thesis director) / Tian, Yanqing (Committee member) / Zhang, Liqiang (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-12
Description
This research looks at a group of students from Tumaini Children's Home in Nyeri, Kenya. The purpose of this paper is to explore why this particular group of students is so academically successful. Quantitative research was taken from the average 2013 test scores of Tumaini students who took the Kenyan Certificate of Primary Education (KCPE) exam in comparison to the scores of students who are not residing in the orphanage. Qualitative research involves interviews from those students who live in Tumaini and interviews from adults who are closely connected to the orphanage. The purpose is to understand why the students are performing so well academically and what support they have created for themselves that allows them to do so.
ContributorsTooker, Amy Elizabeth (Author) / Puckett, Kathleen (Thesis director) / Cocchiarella, Martha (Committee member) / Barrett, The Honors College (Contributor) / Division of Teacher Preparation (Contributor)
Created2014-12
Description
The Latino population is the fastest growing minority group in the United States (U.S Census Bureau, 2003). Such a rapidly changing demographic stresses the importance of implementing strategies into the community social framework to accommodate for cultural and language differences. This research paper seeks to answer: what factors influence the sense of community among Latino families in Phoenix? The following questions will help to assess the dynamic relationship between sense of community and literacy 1) what is the perceived importance of literacy among Latino families living in Phoenix? 2) How is language development reflected among the family dynamics within a predominantly collectivist culture? It is hypothesized that both collectivism and literacy are the main influences on sense of community among this population.
ContributorsBennett, Julie (Author) / Glenberg, Arthur (Thesis director) / Restrepo, Laida (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of International Letters and Cultures (Contributor)
Created2015-05
Description
The research objective is to maintain the A4 nanobody stability during dialysis. Various dialysis buffers were tested and compared, including PBS with varying amounts of the detergent, Tween: low, high, none. Furthermore, PBS, Tris, and HEPES, were tested and compared. PBS without Tween was the worst for preserving A4 stability. PBS was determined to be a better dialysis buffer than Tris or HEPES. To find the optimum buffer, other buffers will be tested and compared with PBS; methods such as gravity filtration and lyophilization will be considered as alternatives to dialysis.
ContributorsTao, Kevin Huang (Author) / Sierks, Michael (Thesis director) / Williams, Stephanie (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
Does assisted cycle therapy influence activities of daily living in older adults with Down syndrome?
Description
The aim of this study is to examine the relationship between Assisted Cycle Therapy, leisure time activity levels, fine motor control, and grip force in older adults with Down syndrome (DS), all of which affect activities of daily living (ADL) and therefore quality of life. This is relevant because this particular group is at risk for developing early onset Alzheimer's disease (AD), which presents itself uniquely in this population. The parent or guardian of six participants with DS completed Godin's Leisure Time Exercise Questionnaire and the participants themselves completed Purdue Pegboard and grip force assessments before and after an 8-week exercise intervention. The results were inconsistent with past research, with no change being seen in fine motor control or grip force and a decrease being seen in leisure activity. These findings are indicative of the importance of the effect of fatigue on leisure activity as well as maintaining elevated heart rate throughout exercise interventions.
ContributorsGomez, Elizabeth Danielle (Author) / Ringenbach, Shannon (Thesis director) / Coon, David (Committee member) / Barrett, The Honors College (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
As prices for fuel along with the demand for renewable resources grow, it becomes of paramount importance to develop new ways of obtaining the energy needed to carry out the tasks we face daily. Costs of production due to energy and time constraints impose severe limitations on what is viable. Biological systems, on the other hand, are innately efficient both in terms of time and energy by handling tasks at the molecular level. Utilizing this efficiency is at the core of this research. Proper manipulation of even common proteins can render complexes functionalized for specific tasks. In this case, the coupling of a rhenium-based organometallic ligand to a modified myoglobin containing a zinc porphyrin, allow for efficient reduction of carbon dioxide, resulting in energy that can be harnessed and byproducts which can be used for further processing. Additionally, a rhenium based ligand functionalized via biotin is tested in conjunction with streptavidin and ruthenium-bipyridine.
ContributorsAllen, Jason Kenneth (Author) / Ghirlanda, Giovanna (Thesis director) / Francisco, Wilson (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2014-12
Description
Understanding glycosaminoglycans’ (GAG) interaction with proteins is of growing interest for therapeutic applications. For instance, heparin is a GAG exploited for its ability to inhibit proteases, therefore inducing anticoagulation. For this reason, heparin is extracted in mass quantities from porcine intestine in the pharmaceutical field. Following a contamination in 2008, alternative sources for heparin are desired. In response, much research has been invested in the extraction of the naturally occurring polysaccharide, heparosan, from Escherichia coli K5 strain. As heparosan contains the same structural backbone as heparin, modifications can be made to produce heparin or heparin-like molecules from this source. Furthermore, isotopically labeled batches of heparosan can be produced to aid in protein-GAG interaction studies. In this study, a comparative look between extraction and purification methods of heparosan was taken. Fed-batch fermentation of this E. coli strain followed by subsequent purification yielded a final 13C/15N labeled batch of 90mg/L of heparosan which was then N-sulfated. Furthermore, a labeled sulfated disaccharide from this batch was utilized in a protein interaction study with CCL5. With NMR analysis, it was found that this heparin-like molecule interacted with CCL5 when its glucosamine residue was in a β-conformation. This represents an interaction reliant on a specific anomericity of this GAG molecule.
ContributorsHoffman, Kristin Michelle (Author) / Wang, Xu (Thesis director) / Cabirac, Gary (Committee member) / Morgan, Ashli (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2015-05