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  The Influence of Staphylococcus Aureus Biofilm associated Gene Mutations on Biofilm Composition

  Bradley Richmond, Courtney Freestone, Emilee Christensen, and Bradford Berges Ph.D.

  Video Presentation 2nd Place Award Winner

  Staphylococcus aureus (biofilms are serious impediments to immune defenses and antibiotics making them a major factor in SA infections. Such infections can be highly lethal despite current treatments, presenting a major challenge to the healthcare industry. Previous genetic screenings of SA have revealed several genes that may be associated with biofilm formation. While many of these genes have been studied, little research has been done to examine how mutations of said genes impact biofilm composition. As several therapeutic options for treating mature SA biofilms require an understanding of the biofilm’s composition, an effort to better comprehend how the genes influence that composition is critical to improving current treatments and developing new ones.

  In this project, we are conducting a study the biofilm phenotypes of the Je 2 strain of SA with mutations in common biofilm associated genes. By comparing the biofilm mass and composition of the wild type Je 2 strain to strains containing mutated biofilm associated genes, we hope to uncover the impact of each mutation on the composition of the biofilm matrix. To make comparisons between mutant biofilms and wild type biofilms, variants of a crystal violet assay are used to determine and characterize biofilm composition.

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  STEMFI Changes Classrooms: Using the Theory of Planned Behavior to Explain Barriers to Change in the STEM Faculty Institute (STEMFI) Professional Development Program

  Jeffrey Shipley, Jamie Jensen PhD, Haley Mickelsen, and Caitlin Playstead

  According to the 2012 PCAST report, only 40% of students who enter college intending to complete a STEM degree are successful in doing so. One of the most common reasons for a student to change majors from a STEM field is the poor quality of instruction. We developed a faculty development program called STEMFI to aid professors in implementing student centered teaching techniques. In order to evaluate the effectiveness of the STEMFI Faculty Institute we performed COPUS analyses before and after an intensive year-long faculty development program.

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  Measuring Alcohol-Induced Secondary Structure Changes of SNAP-25A

  Samuel W. Shumway, Mark T. Parsons, Robert E. Coffman, and Dixon J. Woodbury

  Alcohol has been consumed by humans for thousands of years and has a known inhibitory effect on neurotransmission. Here we explore the effect of ethanol on the folding of SNARE proteins known to drive neurotransmitter release (exocytosis) in neurons. The SNARE proteins SNAP‐25, syntaxin, and VAMP provide the four helical regions (SNARE domains) that form a coiled-coil complex required for exocytosis. This complex is continually formed and unwound as exocytotic vesicles fuse and are recycled.

  Circular Dichroism was used to measure secondary structure of SNAP-25’s first SNARE domain SN1. We observed an increase in α-helical structure followed by precipitation as a ß-sheet when ethanol (EtOH) is added. This is similar to the helical shift observed when SNAP-25 forms a complex with syntaxin and VAMP. These data show that ethanol may induce some of its effects by altering the SNARE fusion machine, consequently playing a role in decreasing neurotransmitter release.

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  Understanding the Changes in Gene Expression Between Stages of Diffuse Large B-Cell Lymphoma

  Rachel Skabelund, Stephen Piccolo, and Kim O'Neill

  In order to understand how cancer progresses from one stage to the next, researchers have been analyzing the changes in gene expression between stages of various cancers. However, very little of this type of research has been done on diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin’s lymphoma that affects 18,000 new patients each year. Using gene set omics analysis (GSOA), we analyzed B-cell specific gene expression pathways in consecutive stages of diffuse large B-cell lymphoma to understand if there were specific pathways that changed their expression from one stage to the next.

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  Macrophage Toll-Like Receptor Chimeric Antigen Receptor: MOTO-CAR™ Shows Potent Activation and Killing of Triple Negative Breast Cancer Cells

  Michelle H. Townsend, Jonathan R. Skidmore, Kelsey A. Bennion, Guoying Wang, Zachary D. Ewell, David Lum, Michael Boyer, and Kim L. O'Neill

  The purpose of this study is to evaluate the efficacy of a mesothelin targeting engineered Macrophage Toll-like Receptor Chimeric Antigen Receptor (MOTO-CAR™). Recently, immunotherapies have emerged as a new horizon for treating cancer. The development of T-cell chimeric antigen receptors (CARs) and their success in treating liquid malignancies transformed the field of cancer treatment, but their effectiveness in treating solid malignancies has been limited due to their inability to traffic to the tumor site. Macrophages, however, are known to be actively recruited by tumors. Due to their association with tumors we chose to explore the use of MOTO-CARS™ as an alternative to CAR T-cell therapy. Murine macrophages were transfected with DNA that expresses the MOTO-CAR™ construct. To validate the ability of engineered MOTO-CARs™ to produce and anti-tumor response, MOTO-CARs™ were challenged in vitro with mesolethin positive breast cancer cells (HCC-1806) where they showed significant cancer regression when compared to mock controls (p-value < 0.0001). To confirm that MOTO-CARs™ polarize to an M1 phenotype following activation, the production of TNF-⍺ post challenge was measured using an ELISA and, when compared to mock controls, a significant increase in the production of TNF-⍺ was observed (p-value =0.0093). Finally, the efficacy of MOTO-CARs™ were evaluated in vivo using an NSG mouse model. After administering cells via tail-vein injection, we observed that MOTO-CARs™ trafficked to tumor sites and generated a significant reduction in tumor size (p-value = 0.0006). In conclusion, we report that macrophages, engineered with toll-like receptor-chimeric antigen receptors show strong promise in the battle against solid malignancies.

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  Galectin-1: A Potential Protein Therapy for Limb-Girdle Muscular Dystrophy 2B

  Mary L. Vallecillo, Matthew S. Teynor, Jonard C. Valdoz, Spencer D. Hayes, P. Daniel Poulson, Matthew F. Rathgeber, Sean R. Stowell, and Pam M. Van Ry

  • Limb-Girdle Muscular Dystrophy 2B (LGMD2B) belongs to a group of diseases called dysferlinopathies, caused by mutations in the DYSF gene.
  • Dysferlin is an important muscle membrane protein involved in repair and regeneration after injury.
  • LGMD2B causes muscle wasting, fat infiltration, and loss of ambulation in patients.
  • Currently there is no cure and few treatment options.
  • Galectin-1 is a small protein that interacts with glycosylated proteins. It shows efficacy in treating murine models of Duchenne Muscular Dystrophy.
  • Here we explore the ability of recombinant human Galectin-1 (rHsGal-1) to ameliorate disease pathologies and mechanisms of LGMD2B

  Hypothesis: Recombinant human galectin-1 (rHsGal-1) protein treatment will improve membrane repair of LGMD2B models thus increasing myogenesis, stabilizing muscle integrity, and decreasing disease manifestation.

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  Sunflower Seedlings Fail to Remove Uranium in the Navajo Nation

  Zak Webber and Ben Abbott

  Mining and the natural geology in the Navajo Nation has led to widespread pollution of uranium contaminating the livestock and drinking water of many Navajo. Uranium has been shown to have adverse health effects and be connected withhypertension, renal failure, and cancer.

  Recent studies suggested that the common sunflower, helianthus annus, has the ability to remove uranium in a hydroponic (water only) environment. This led us to believe that sunflowers may be effective to remove uranium from the water in soil conditions in the Navajo Nation.