SPUR Participants

Summer 2017 Participants

Jake Becker, Salt Lake Community College (Prof. Christie Toth, Writing & Rhetoric Studies)

Urban Writing Ecologies: Mapping Inter-Instituional Writing Transfer 

As of 2014, 7.3 million students were enrolled for credit in the nation’s 1,108 community colleges. That is roughly 45% of all U.S. postsecondary students, and 41% of first-time, first-year college students (AACC). Approximately 80% of incoming community college students say they plan to earn a bachelor’s degree. Yet only 25% actually transfer to a four-year institution within five years, and just 17% earn a bachelor’s degree within six years of transferring (Jenkins and Fink). In light of these figures, our research is locally situated on student transfer between Salt Lake Community College (SLCC) and the University of Utah (UofU), specifically how students adapt writing knowledge across institutional settings. Currently, there has been very little research on how students transfer writing knowledge between postsecondary institutions (Gere et al.). Drawing upon ecological theories of writing, the goal of this research is to increase the pedagogical approaches for fostering successful student writing transitions, while simultaneously bolstering successful student transfer between SLCC and the U of U. To accomplish this, we have curated two pilot courses within the Department of Writing & Rhetoric Studies, with the goal of developing resources for incoming transfer students. Our research provides new insight on the value of prior knowledge for understanding and navigating new writing contexts, while also showcasing key meta-concepts that facilitate successful writing transfer.

Matt Conley, Brigham Young University (Prof. Jared Rutter, Biochemistry)

Stress Responsive Degradation of mRNA Encoding Mitochondrial Proteins.

The degradation of cytosolic mRNA is crucial to the regulation of gene expression and can be induced by numerous cellular perturbations including glucose deprivation, etc. Although many stressors are known, cytoplasmic mRNA degradation has never been studied in the context of organellar stress. Recent studies have demonstrated that mitochondrial protein import stress activates a cytosolic response that leads to the degradation of proteins bound for the mitochondria. However, in the context of a similar stress, there remains nothing known regarding the fate of cytoplasmic mRNA encoding mitochondrial proteins. Thus, we sought to study mitochondrial stress induced mRNA degradation. In order to assay the induction of mRNA degradation, we engineered several Saccharomyces cerevisiae strains, in which GFP was fused to proteins involved in mRNA decapping and degradation. The accumulation of these proteins in subcellular structures termed p-bodies is commonly used to assay active mRNA degradation. We hypothesized that the accumulation of p-bodies would increase in response to mitochondrial stress. In order to induce stress, we chose two methods. First, we treated the cells with small molecules that uncouple the mitochondrial membrane and disable mitochondrial protein import. Second, we used FASII mutant strains, thereby creating a genetic model of mitochondrial stress. In order to assess p-body accumulation, we have employed fluorescent microscopy. Furthermore, we will perform RNA-seq assay and measure the levels of mRNA encoding a subset of mitochondrial proteins and compare the results to the level of said mRNA levels when mitochondrial stress is induced.

Kelly Corbray, University of Utah (Prof. Christie Toth, Writing & Rhetoric Studies)

Urban Writing Ecologies: Mapping Inter-Instituional Writing Transfer 

As of 2014, 7.3 million students were enrolled for credit in the nation’s 1,108 community colleges. That is roughly 45% of all U.S. postsecondary students, and 41% of first-time, first-year college students (AACC). Approximately 80% of incoming community college students say they plan to earn a bachelor’s degree. Yet only 25% actually transfer to a four-year institution within five years, and just 17% earn a bachelor’s degree within six years of transferring (Jenkins and Fink). In light of these figures, our research is locally situated on student transfer between Salt Lake Community College (SLCC) and the University of Utah (UofU), specifically how students adapt writing knowledge across institutional settings. Currently, there has been very little research on how students transfer writing knowledge between postsecondary institutions (Gere et al.). Drawing upon ecological theories of writing, the goal of this research is to increase the pedagogical approaches for fostering successful student writing transitions, while simultaneously bolstering successful student transfer between SLCC and the U of U. To accomplish this, we have curated two pilot courses within the Department of Writing & Rhetoric Studies, with the goal of developing resources for incoming transfer students. Our research provides new insight on the value of prior knowledge for understanding and navigating new writing contexts, while also showcasing key meta-concepts that facilitate successful writing transfer.

Ali Dibble, University of Utah (Prof. Taylor Sparks, Materials Science & Engineering)

Evaluating Performance of Sustainable Materials and Design in Feminine Hygiene Pads

Disposable feminine hygiene products are typically made with synthetic materials and chemical additives, which create a tremendous amount of waste that takes nearly a century to degrade under landfill settings. Several companies sell products to mitigate these environmental concerns, but these products are either not completely biodegradable or are bulky and uncomfortable to the user due to a large quantity of cellulose fiber added for absorbency. This project aims to assess the differences in absorbent capabilities between industry products and proposed biodegradable alternatives to determine if a biodegradable product can be created without sacrificing absorbency or user comfort. It is found that biodegradable hydrogels are 4 times less absorbent than industry-processed hydrogels. Boiled cotton is not a sufficient processing method as it only absorbs 45% the amount of fluid as chlorine-bleached cotton, though sustainable H2O2-bleached cotton absorbs 113% the amount of fluid as industry cotton. Preliminary fiber alignment patterns are also investigated to maximize fluid flow through the product and compensate for inferior material performance.

Chance Fox, Brigham Young University (Prof. Jeffrey Anderson, Radiology)

Why so Atypical: Typicality of the Default Mode Network as a Measure of Social Function in Autism Spectrum Disorder

The extreme heterogeneity in both symptoms and severity of autism spectrum disorder (ASD) has proven an obstacle to establishing coherent neurophysiological criteria for improving diagnosis and treatment options. Brain MRI measurements in autism have been similarly heterogeneous, and specific differences have not been found to be reliable clinical predictors of severity or prognosis. Functional connectivity MRI evaluates synchronized brain activity to measure relationships between brain regions, estimating a “wiring diagram” for the brain. We hypothesized that the similarity of functional connectivity to mean values across a typically developing population (typicality) might be a useful biomarker for autism that is less sensitive to autism heterogeneity. We used two analyses, {1} a principal component (PC) analysis and {2} a dynamical simulation of brain network activity, to compare typicality of functional connectivity to social function. We calculated principal components of connectivity between 25 million pairs of brain regions and compared principal components from each individual’s connectivity in a large (n=487 autism, n=646 control subjects) cohort of autism and control individuals to average values from the Human Connectome Project (n=820 typically developing subjects). We found that nine out of the first ten PCs represented in control subjects were significantly more similar to typically developing population averages than ASD subjects were. For one of these components, which represented the brain’s default mode network that processes attention to one’s internal thoughts, the atypicality of this component for each autism subject compared to population means correlated with the degree of social dysfunction they exhibited (p=0.0000093). A simulation of brain network convergence to the default mode network revealed that an atypical convergence pattern is also indicative of increased social dysfunction (p=.0012). These findings suggest that typicality is a potential measure of social function in ASD, and possibly other neuropsychiatric disorders.

Fadi Haroun, University of South Dakota (Prof. Alana Welm, Oncological Sciences)

Understanding the Mechanism of Tumor Remission in Response to a Novel Immunotherapy Treatment for Breast Cancer

Cytotoxic T Lymphocytes (CTL) have an important role in eliminating cancer cells. The immune system has mechanisms to deactivate these cells to prevent excessive inflammation. This deactivation is mainly done through receptors on the surface of the CTL called checkpoint molecules. However, these molecules are often exploited by cancer cells to avoid eradication by the immune system. Based on this, checkpoint blockade has been studied as a method of achieving immune activation to promote CTL function in fighting cancer cells. Checkpoint blockade has been shown to be effective in many clinical trials, where patients who responded to the treatment had durable responses. However, many patients did not respond to this treatment. Therefore, combination of checkpoint blockade with other treatments has emerged as a possible method to potentiate an immune response in more patients. Ron is a receptor tyrosine kinase known to suppress the immune response through several mechanisms such as the attenuation of inflammatory response by promoting M2 macrophage state, and the downregulation of IL-12, among other mechanisms. In addition, Ron is linked to the immune checkpoint axis since Ron activation can upregulate PD-L1 and CD80 checkpoint molecules. Therefore, we combined a checkpoint blocking antibody (anti-CTLA4) with a Ron tyrosine kinase inhibitor to block the suppression of the immune system on two different levels in a mouse model of breast cancer. The combination showed significantly higher response rates compared to the monotreatment. This project was aimed at understanding the mechanism by which this novel treatment improved response rates. Since tumor infiltration by CTLs is an important component of the cancer immunity cycle, we specifically investigated whether our novel treatment caused more tumor infiltration, by immune staining and analysis of endpoint tumor samples. Our combination treatment showed significant increase in tumor infiltration compared to vehicle-treated mice, but there was no significant difference from the monotreatment.

Sydney Lambert, Vassar College (Prof. Alex Shcheglovitov, Neurobiology)

The Regulation of Shank3 in the Absence and Presence of Different Deletions

Phelan McDermid Syndrome (PMDS) is a rare genetic disorder linked to autism that comes with a suite of phenotypes, including decreased muscle tone, developmental delays, and intellectual disabilities. PMDS occurs when the terminal end of chromosome 22 is deleted. This terminal deletion disrupts the function of the gene Shank3. Shank3 is a complex gene that codes for a scaffolding protein in the postsynaptic density. The Shank3 protein coordinates synaptic function and is mainly found in the brain. Its location poses an ethical barrier that prevents direct study. To get around the dilemmas of obtaining live brain tissue, we utilized induced pluripotent stem cells (iPSCs) to grow genetically identical neurons starting from less invasive, less critical tissue. After establishing these lines of neurons from patients with no Shank3 deletion, we employed a CRISPR/Cas9 system to introduce two specific deletions that we wanted to study: one complete heterozygous deletion and one partial homozygous deletion (Table 1). We suspected that the regulation of Shank3 would be changed in the presence of deletions. To test this, we designed promoter-specific sets of primers to target each of the sites that can produce unique isoforms. We then ran PCR and gel electrophoresis to identify the resulting isoform lengths. Preliminary results showed possible deletion-dependent regulation of Shank3. Understanding the regulation of Shank3 in the presence of different deletions will contribute to the overall knowledge of how genetic mutations create a plethora of observed phenotypes.

Billy Jeon, Rice University (Prof. Luke Timmins, Bioengineering)

Design and Construction of a Computer-Controlled Biaxial Testing Device for Vascular Tissue

Cardiovascular disease continues to be the leading cause of death in the world, and there is a clear need for research in this area. Exploring the biomechanics of the cardiovascular system, particularly arterial tissue, plays a key role in better understanding the pathogenesis of diseases, which would ultimately lead to better diagnosis and treatment options. Herein, we present the design and development of a computer-controlled, electromechanical biaxial testing device which can simultaneously apply pressure cycles (inflate) and axially stretch (extend) excised arteries. The device consists of four major parts: motion control (via 3-axis stages, motorized actuators, and modular posts), pressure control (via syringe pump and pressure transducer), imaging (monochrome CCD), and computer automation (via programming in LabVIEW). These components allow for the cyclic pressurization at multiple axial stretches, providing pressure/diameter and load/length curves. We tested our device with excised porcine carotid arteries. Data demonstrate a non-linearly elastic behavior under loading, which is commonly observed for soft biologic tissues. Through these experiments, we can better characterize the mechanical behavior of arterial tissue and understand how tissue responds to physiologic and pathologic loading conditions.

Raquel Maynez, University of Utah (Prof. Mike Shapiro, Biology)

MOLECULAR EFFECTS OF A CODING MUTATION IN A PIGMENTATION PATTERNING GENE

Color patterns in birds and other vertebrates are incredibly diverse and can impact fitness by affecting mate choice, crypsis, and survival. However, the genetic and developmental basis of this diversity is not well understood. In order to investigate pigmentation patterning variation, our lab studies the domestic pigeon. Domestic pigeons are immensely diverse in many traits, including pigmentation patterns. All pigeons have one of four major wing pigmentation patterns: T-check, checker, bar, or barless. Barless is the most recessive phenotype, characterized by a lack of the ancestral bars on the wing and an increased incidence of vision defects. Previously, the Shapiro lab found that variation in a gene that encodes a secreted protein is associated with the major wing pigmentation patterns. All barless birds are fixed for a start codon mutation that truncates the protein by 13 amino acids, shortening the signal peptide sequence. We are currently assessing whether this mutation effects secretion of the protein. In order to do this, we have begun constructing a mutant, wild type, and no signal sequence version of the gene with fluorescent tags, the latter two serving as controls for comparison to the mutant. We will then transform each construct into HeLa cells and visualize cellular localization of the tagged proteins using microscopy. We will also separate the supernatant (extracellular fluid) and cells of a liquid culture and use western blots to evaluate whether the protein was secreted into the supernatant or remained in the cells for all three constructs. I hypothesize that the mutant will have reduced secretion because of the shortened signal sequence. By collecting and examining our findings, we will gain insight into the molecular basis of pigmentation patterns found in pigeons and potentially gain insight into similar phenotypes found in wild bird species.

Johanna Mora, University of Texas Rio Grande Valley (Prof. Daniel Leung, Infectious Disease)

Optimizing Growth Conditions for Clonal Expansion of Mucosal-Associated Invariant T (MAIT) Cells

Mucosal-associated invariant T (MAIT) are innate-like T-cells that recognize microbial riboflavin metabolites presented by the highly conserved MR1 (MHC class-I Related) molecule. In humans, MAIT cells account for up to 10% of the peripheral blood T cells, and are enriched in the intestine and liver. The clonality, function, and activity of MAITs cells are not well understood. In preliminary experiments, we have found significant functional heterogeneity across different clonotypes. Current methods for expansion of MAIT clones are not well established, and the optimal conditions for cloning MAIT cells are not known. Here, we examine different conditions to determine which are optimal for expansion of MAIT cells. We compared various concentrations and presence of cytokines IL-2, CD3/CD28, and TGF-b. Results are pending at time of this abstract. Determining optimal growth conditions for expanding individual MAIT clones will be essential for better understanding their biology. Our lab is interested in using these techniques to clone MAITs from healthy and infected (HIV and cholera) donors to evaluate their plasticity and functional characteristics.

Vinny Morrow, Waynesburg University (Prof. Micah Drummond, Physical Therapy)

Skeletal Muscle Insulin Sensitivity and Cell Stress Signaling during Reduced Activity and Recovery in Older Adults

The Drummond laboratory has previously shown that signaling through the innate immune system contributes to the inflammatory response, ceramide biosynthesis, and metabolic disruptions such as impaired glucose uptake and insulin resistance. These physiological changes are allied with short term skeletal muscle inactivity in hindlimb unloading mice and healthy older adults on bed rest. These models are intended to be representative of short term periods of physical inactivity in older adults resulting from injury or disease that progresses to atrophy, sarcopenia, dynapenia, and eventually, functional dependency. Although insulin insensitivity and muscle atrophy are common in strict bed rest, often hospitalization does not entail strict bed rest and instead hospitalization and recovery in the following weeks can be characterized by reduced physical activity through a reduction in total daily steps. Therefore, we collected muscle biopsies from healthy older adults before (pre) after 2 weeks of step reduction (RA: <75% of normal activity) and 2 subsequent weeks of recovery (REC: return to baseline activity levels). Muscle samples were lysed and run through SDS-PAGE and transferred to a PVDF membrane for assessment of proteins expression related to insulin sensitivity, cell stress and ceramide biosynthesis pathways This will give insight if the insulin insensitivity and muscle atrophy following a period of step reduction are associated with the TLR-4/MyD88 signaling pathway.

Arthy Narayanan, BMS College of Engineering (Prof. Al Light, Anesthesiology)

Detection of Gene Variants in Chronic Fatigue Syndrome Patients

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are chronic conditions often present in the same patient, characterized by severe physical fatigue, widespread muscle and joint pain, mental fog and post-exertional worsening of symptoms. Patients with ME/CFS and FM experience difficulty in performing daily activities and in some cases are wheelchair-bound. In a pilot sample, the majority of ME/CFS patients had elevated autoantibodies to autonomic receptors and also showed variants (mutations) in genes linked to cellular energy (mitochondria). This study aims to identify some of the gene variants that may contribute to ME/CFS and FM by comparing the genetic sequences of these patients with that of the controls. Our hypothesis is that ME/CFS is both an autoimmune disorder and an energy deficiency disorder, so we have focused on both immune and mitochondrial/energy genes. Blood samples were drawn from ME/CFS patients and controls and the leukocytes were separated from it. The mRNA of these leukocytes, which represents the transcriptome of the cells, was extracted and then sequenced using the RNA-Seq method. The mutations in the genes were ranked as low, moderate or high impact on the function of the gene. In this initial sample of 44 of the planned 340 participants, we identified 3 automunity/immune function variants (LILRA6, RFTN1 and MARCH8) and several different multigene patterns for mitochondrial variants with moderate and high impact that occurred with greater frequency in the ME/CFS patients vs. controls. When the data from all 340 participants is complete, it will help identify biomarkers to make diagnosis easier and may also provide targets for developing new treatments for ME/CFS and FM.

Valeria Ortiz Torres, University of Puerto Rico, Mayaguez Campus (Prof. Matthew VanBrocklin, Surgery)

Development and testing of an immune receptor identification system to discover novel receptors for immune signaler, B7H3

Recently, therapies involving immune reactivation have held great promise for melanoma patients. Many of these immunotherapies include immune checkpoint inhibitors or blocking antibodies which reactivate the immune system by removing the malfunctioning brakes on T-cell function. For example, CTLA4 and PD1-targeting antibodies used together in Phase III clinical trials have resulted in tumor diminishing responses in up to 60% of patients. Although responses for combined blockade with CTLA4 and PD1 antibodies have been successful, there are up to 40% of patients which do not respond and additional means for immune activation need to be explored. Our goal in this summer research project has been to develop tools and begin testing the immune nature of the B7H3 signaling molecule and identify its receptors. Importantly, we seek to discover receptors for B7H3 involved in immune suppressive signals which may be targeted for immunotherapy blockade. B7H3 is in the same family as PD-L1 (aka. B7H1) which is the signaling ligand of the PD1 checkpoint receptor and thus is a likely target for successful immune checkpoint blockade. We have been testing eighteen different genes and their protein products in HEK293FT cells to identify binding interactions with B7H3. In this first phase of the overall project we have cloned the genes to be tested into expression vectors, performed E.coli transformations, made large-scale preps (maxi preps) of each DNA plasmid, transfected HEK293FT cells, and given B7H3 treatment and performed flow cytometry to measure binding and assess potential receptors identified.

Hannah Peterson, Belmont University (Prof. Christopher Reilly, Pharmacology & Toxicology)

Elucidation of Amino Acids Regulating the Species-Selective Activation of TRPM8 by Coal Fly Ash Particles

Transient receptor protein melastatin-8 (TRPM8) is an ion channel expressed by neurons and epithelial cells in the lungs. TRPM8 is activated by cold temperatures and soluble agonists that produce a “cooling” effect. Human TRPM8 is also activated by particulate matter, specifically coal fly ash (CFA), a calcium-rich material produced from burning coal. Exposure to CFA has been associated with adverse health effects on the respiratory system. When treated with CFA, human bronchial epithelial cells showed an induction of pro-inflammatory cytokines while instillation of CFA into mouse lungs showed minimal pro-inflammatory effects. Additionally, mouse Trpm8 was not activated by CFA. The goal of this project was to determine amino acids within the TRPM8 protein responsible for species-selective activation by CFA. Within the pore loop region of the TRPM8 protein, three residues (921,927, and 932) differed between human and mouse TRPM8. Site-directed mutagenesis was used to introduce corresponding amino acid changes.The mutant TRPM8 plasmid DNA was then transfected into human HEK-293 cells overexpressing the calcium-sensitive reporter gene GCaMP6s.Calcium flux assays were used to determine the activity of the mutant TRPM8 proteins relative to the respective wild type forms. The hG921S human to mouse mutation had little effect on human TRPM8 activity, but the corresponding mS921G mouse to human mutation increased activity compared to the wild-type mouse TRPM8; however, the response was only ~50% that of human TRPM8. The hA927S did not change responses of human TRPM8, but the mS927A exhibited responses comparable to wild-type human TRPM8.Finally, the hT932S and mS932T mutants were both inactive, similar to wild-type mouse TRPM8.These results reveal specific residues on the pore loop region of TRPM8 that regulate its activation by CFA. These findings improve our understanding of how TRPM8 is activated by particulate materials which will facilitate studies into its contribution to lung pathologies by providing the opportunity to develop new genetically modified mouse models.

Jose Porras, University of Texas Rio Grande Valley (Prof. Jason Shepherd, Neurobiology)

GENERATING SYNAPTIC REPORTERS FOR UNDERSTANDING MEMORY STORAGE

Understanding how memories are stored is essential to understanding Alzheimer’s Disease as well as normal cognition. In the early 20th century, Richard Semon proposed the engram hypothesis, that connections between neurons were made as a result of stimulation. Recent studies support this hypothesis. However, when the encoding of various events occurs within two hours, these circuits can show overlap, suggesting the engram is not limited to whole cells. We hypothesize that the most basic form of the engram is one distinct set of synapses. To test this, we are developing SLAyR (synaptically localized activity reporter), a genetic tool designed to only label active synapses. We are doing this by modifying FingR (fibronectin intrabody generated with mRNA display), a probe that binds to PSD95, a scaffolding protein found in excitatory synapses. The modifications we plan to make, if successful, will limit binding to only PSD95 in active synapses. This can be achieved by adding a few selected components cloned from Arc (activity regulated cytoskeletal protein). These include an activity dependent enhancer and Arc’s UTR (untranslated region). The activity dependent enhancer will regulate transcription of SLAyR to only active neurons while the 3’UTR will guide the mRNA to active synapses. Further activity will then promote the translation of this mRNA, which will bind to PSD95 in these active synapses where the protein was synthesized. I am assisting in this project by cloning versions of SLAyR with different enhancers and a smaller Dendritic Targeting Element in lieu of using the whole UTR. We are then testing these constructs in cultured neurons to verify that they are showing activity dependent expression and labeling only active synapses. Once the active synapses are targeted, we can elucidate changes in protein and cytoskeletal organization that are associated with memory. SLAyR will be an invaluable tool to guide us closer to understanding the molecular mechanism of memory storage, helping us develop better ways to treat conditions like Alzheimer’s Disease.

Mu Pye, University of Utah (Prof. Akiko Kamimura, Sociology)

Patient Satisfaction and Perspectives of Continuity of Care among Free Clinic Patients in the USA

Free clinics are important resources for those who un- or under insured individual in the United states. The purpose of this study was to explore continuity of care and patient satisfaction from the perspectives of free clinic patients. Since the majority of free clinic providers are volunteers and may not be with a free clinic long-term, continuity of care should not be just seeing the same doctor over time, but also seeing well-coordinated providers. Because free clinics serve a wide variety of underserved populations, cultural competence training in medical education may not wholly t the socioeconomic and/or cultural realities of free clinic patients. And the result of continuity of care was not always perceived positively. There were potential miscommunications between providers or receptionists and patients. Patients may not be well informed of the available resources at the clinic. More in-person communication would be beneficial to distribute the information about available resources for free clinic patients. Communication among patients and receptionists, providers, and interpreters seemed to be a prevalent recurring topic across groups. The communication of health programs and appointment reminders are the areas to be improved. Training in communications with patients or cultural competence in medical education may need to consider a wide variety of patient backgrounds.

Michael Ruesch, Brigham Young University (Prof. Randy Jensen, Neurosurgery)

Knockout of hypoxia induced factor 1α in meningioma and glioma cell lines via short hairpin RNA interference and the CRISPR-Cas9 system

Introduction: Hypoxia, a decrease in oxygen perfusion from homeostatic levels, is common in a variety of primary brain tumors including meningiomas and gliomas. It has been found to correlate with more aggressive tumor growth, development of both meningiomas and gliomas, regulation of tumor microenvironment, as well as diffusion restriction and necrosis. Hypoxia-Inducible Factors (HIFs), specifically HIF-1α, are upregulated under hypoxic conditions and after radiation treatment, leading to a greater radioresistance in tumors. Previous work in our lab utilized a HIF-1α shRNA knockdown in a glioma primary cell model, which has been unsuccessfully produced in primary meningioma cells. Methods: A lentiviral-based clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 construct was used to generate a HIF-1α knockout in a primary human meningioma cell line (GAR). Viral particles were generated in Hek 293T cells. Verification of the transfection was performed using green fluorescence protein (GFP) analysis, morphological analysis of cells, and evaluation of cell proliferation dynamics. An adenovirus-mediated HIF-1α targeting shRNA was also developed and compared. Results: We have generated successful plasmid and concentrated viral particle as verified by GFP expression in Hek 293T cells and infected GAR cells. Generation of a HIF-1α targeting shRNA adenovirus was verified by immunofluorescence analysis of virus producing Hek 293T cells and PCR analysis of generated plasmids. Quantitative analysis of HIF-1α levels was determined via a HIF-1α based ELISA to determine knockout efficiency. Discussion: We successfully created a lentivirus-CRISPR/Cas9 and adenovirus-shRNA knockout model for HIF-1α. Further work will include in vitro characterization of infected cells and in vivo treatment of meningioma and glioma animal models. The impact of radiation on HIF-1α knockout cells will be evaluated. These results will aid in the understanding of HIF-1α on meningioma and glioma dynamics, as well as the impact of radiotherapy.

Abby Scott, Westminster College (Prof. Eric Schmidt, Medicinal Chemistry)

Optimizing Cyclization of Peptides for Use on Drug Analogs

Conotoxins, peptides found in cone snail venom, have a variety of potential pharmaceutical applications, such as a treatment for cocaine and nicotine addiction. Some difficulties with using peptides as pharmaceuticals are their large size and instability when linear. PatG and TruD, enzymes found in symbionts of the ascidian Lissoclinum patella, can be used to cyclize peptides. The purpose of this project was to optimize the cyclization of conotoxin peptide fragments for use as drug analogs. This was accomplished by assessing the cyclization activity of TruD, PatG, and a S783C PatG mutant in different combinations on 4 test substrates. Liquid Chromatography Mass Spectrometry (LCMS) was used to assess the resulting peptide structures in each of the assays.

Konrad Serbinowski, University of Utah (Prof. Taylor Sparks, Materials Science & Engineering)

Discovery and Synthesis of Superhard Materials

Superhard materials are materials which have a Vickers’s hardness measurement exceeding 40 gigapascals. Currently the most well-know superhard material is diamond, but like most other superhard materials, diamond requires high temperature and pressure to synthesize which leads to high production costs. A promising solution to this is the synthesis of superhard materials which do not require high pressure for synthesis. Most of these materials are heavy transition metal borides and carbides which do not need to form as many short covalent bonds due to the layers of heavy transition metals which have d-valence electrons. Through the use of machine learning we are able to identify the best superhard materials which have low production cost and then cross check with HHI values and other economic factors in order to ensure the possibility of production on a larger scale.

Joseph Sheikh, University of Utah (Prof. Sophie Caron, Biology)

Mapping Gustatory Sensing Neural Circuits in Drosophila

A key question that remains unanswered in the field of neuroscience is how the brain combines different types of sensory information and generates a meaningful representation of the outside world. The Caron laboratory investigates how the Drosophila melanogaster brain, in particular the mushroom body, integrates sensory information. The first step in understand multimodal integration is understanding neural circuits, therefore the research conducted was to determine whether either the GR64f+ sweet sensing neurons, GR66a+ bitter sensing neurons, or ppk28+ water sensing neurons connect to gustatory projection neuron (gPN1). It was hypothesized that these connections exist due to anatomical evidence from previous research. In order to verify connections between the two neurons, GFP Reconstitution Across Synaptic Partners (GRASP) and fluorescent protein tdTomato were used to mark the neurons, then imaged using confocal microscopy. The results of this experiment have revealed a potential connection between GR64f+ and ppk28+ with gPN1; however, further data is needed to make a conclusion.

Kai Sin, University of Utah (Prof. Akiko Kamimura, Sociology)

Patient Satisfaction and Perspectives of Continuity of Care among Free Clinic Patients in the USA

Free clinics are important resources for those who un- or under insured individual in the United states. The purpose of this study was to explore continuity of care and patient satisfaction from the perspectives of free clinic patients. Since the majority of free clinic providers are volunteers and may not be with a free clinic long-term, continuity of care should not be just seeing the same doctor over time, but also seeing well-coordinated providers. Because free clinics serve a wide variety of underserved populations, cultural competence training in medical education may not wholly t the socioeconomic and/or cultural realities of free clinic patients. And the result of continuity of care was not always perceived positively. There were potential miscommunications between providers or receptionists and patients. Patients may not be well informed of the available resources at the clinic. More in-person communication would be beneficial to distribute the information about available resources for free clinic patients. Communication among patients and receptionists, providers, and interpreters seemed to be a prevalent recurring topic across groups. The communication of health programs and appointment reminders are the areas to be improved. Training in communications with patients or cultural competence in medical education may need to consider a wide variety of patient backgrounds.

Shane Tory, University of Utah (Prof. Taylor Sparks, Materials Science & Engineering)

A New Sodium Ion Conductor: Processing and Transport Relationships

Sodium based electrochemical cells are gaining interest in industry due to the high availability and abundance of sodium. A sodium ion conducting electrolyte is one essential component of an electrochemical cell. Sodium zirconium gallate (Na0.7Ga4.7Zr0.3O8) belongs to the beta gallate rutile structure type and was recently discovered. Preliminary measurements show it to be a one-dimensional sodium ion conductor. In a similar process, synthesis of Na-β”-alumina + 3 mol.%Y2O3-stabilized zirconia (YSZ) by a vapor phase process lead to a textured microstructure with accompanying anisotropic transport. Here, we report on the synthesis of Na0.7Ga4.7Zr0.3O8 + YSZ composites by a vapor phase process and observe no evidence of crystallographic texturing or anisotropy in ionic transport. In addition, the kinetics of vapor phase transformation in Na0.7Ga4.7Zr0.3O8 + YSZ composites were studied. The results showed a similar trend to the kinetic of previously studied Na-β”-alumina + YSZ composites suggesting a similar oxygen transport rate limiting mechanism of transformation.

Tyler Vail, Brigham Young University (Prof. KC Brennan, Neurology)

2-photon Microscopy Analysis of Neuronal Ca2+ Activity During Cortical Spreading Depression After Traumatic Brain Injury

Traumatic Brain Injury (TBI) is frequent among civilian and military personnel. TBI can result from car crashes, sports, violence, or blast injuries. Despite its relevance, the long-term effects of TBI are not fully understood. Spreading depolarization (SD) is a wave of excitation that passes through the brain that occurs at the time of and following TBI which may exhibit long term effects on brain tissue and cortical networks. The goal of our research is to investigate cellular changes after a traumatic brain injury. Controlled Cortical Impact (CCI) is a well-documented technique that can be used to replicate the injuries similar to TBI. We used CCI combined with two-photon microscopy to observe calcium levels during SD to detect changes on a cellular level. These changes suggest that TBI may be more serious than we thought because of increased damage due to spreading depolarizations.

Lacey Woods, Southern Utah University (Prof. Peter West, Pharmacology & Toxicology)

The Effects of Spontaneously Recurrent Seizures on Dentate Gyrus-Mediated Cognitive Function and Synaptic Plasticity in the Intra Amygdala Kayanate Model of Temporal Lobe Epilepsy

Seizures associated with epilepsy often result in cognitive comorbidities, such as memory loss, that still remain medically untreated. Mouse models have been useful in developing drugs to stop seizures in epileptic patients but not to treat the cognitive comorbidities that significantly affect the patient’s quality of life. Commonly used electrically-induced acute seizure models, such as the corneal kindled mouse model of focal seizures, have been shown to have impaired dentate gyrus (DG) mediated spatial pattern processing, learning, memory, and attenuated DG synaptic plasticity (Remigio et al., 2017). However, in the effort to develop treatments of cognitive comorbidities in epilepsy, more advanced models are needed that experience genuine spontaneous recurrent seizures (SRSs) and cognitive dysfunction. Therefore, the aim of this experiment is to evaluate the effects of SRSs on dentate gyrus-mediated cognitive function and synaptic plasticity in a novel model of temporal lobe epilepsy: the intra-amygdala kainate mouse (IAK) (Almeida Silva et al., 2016; Mouri et al., 2008). After a latent period of approximately 3-5 days, a cohort of the IAK mice was shown to experience approximately 1-2 spontaneous seizures per day (n=10). When tested in a task reliant on spatial pattern processing in the dentate gyrus (the metric task), these IAK mice were shown to have significant learning and memory impairments compared to the SHAM surgical and control mice. Finally, in a measure of experience-dependent synaptic plasticity commonly accepted as a model of learning and memory at the level of the synapse (Long-Term Potentiation, LTP), LTP at the perforant path – dentate granule cell synapse in the IAK group was significantly attenuated relative to both the control and SHAM surgical mice. These results strongly suggest that SRSs significantly impact cognitive function both in vivo and in vitro at the level of the dentate gyrus. Therefore, IAK mice may be useful as a tool to evaluate novel treatments for cognitive dysfunction associated with SRSs in patients with epilepsy.