Life Sciences Commons^™

Investigating Human Follicle Stimulating Hormone Receptor And Its Partners Using The Apex Assay, Alexandra Temple

Honors Theses

Many men and women deal with fertility whether it’s needing infertility treatments or contraceptives. The follicle stimulating hormone (FSH) and follicle stimulating hormone receptor (FSHR) play important roles in reproduction and fertility in both males and females. Fertility issues can arise when interactions between FSH and FSHR aren’t functioning properly and FSHR signaling is disrupted. FSHR is a G-protein coupled receptor (GPCR) found on the cell surface of granulosa cells in women and Sertoli cells in men. Activated FSHR initiates a cascade of downstream signaling events that result in different biological effects such as ovarian follicular development and estrogen production …

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz

Honors Theses

Malignant breast cancers exhibit preferential metastasis to bone and lung (1). While changes in gene expression in lung-specific (LM) and bone-specific metastasis (BoM) lines derived from the MDA-MB-231 breast cancer line have been identified, few metabolic genes are differentially expressed; thus it is unknown if tissue-specific metabolic reprogramming occurs. Two hallmarks of cancer cells are an altered metabolic phenotype characterized by enhanced conversion of glucose to lactate in spite of adequate oxygen availability for complete mitochondrial oxidation of this substrate (referred to as aerobic glycolysis or the Warburg effect) and a greater dependence on glutamine. These changes in primary tumor …

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products), which bind …

Elucidating The Functional Location Of Platelet-Derived Growth Factor Receptor Alpha, Creation Of A Review Chapter On The Use Of Zebrafish In Studying Congenital Heart Defects, And Using 3d Printing To Create Laboratory Tools, Jaret Lieberth

Honors Theses

Congenital heart defects (CHDs) are currently the most prevalent form of birth defect in the United States. Their combined frequency and severity make necessary a deeper understanding of the molecular underpinnings guiding heart formation. The first major step in cardiac morphogenesis, cardiac fusion, involves the medial movement of bilateral populations of myocardial precursor cells to the embryonic midline, where they merge to form the primitive heart tube. Although crucial to subsequent organogenesis, the precise mechanisms governing cardiac fusion remain unknown. Previous studies have found that a mutation in platelet-derived growth factor receptor alpha (pdgfra), called refuse-to-fuse (ref), results …

Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell

Honors Theses

Metastasis is responsible for the majority of cancer related deaths. In breast cancer the lungs and bones are the major sites for metastasis. Previous studies used the metastatic aggressive MDA-MB-231 breast cancer line to isolate sub-clones that preferentially invade the lungs (LM line) or bones (BoM line). While genes associated with the tissue specific metastasis have been identified, it is unknown if metabolic adaptations contribute to the growth of the LM and BoM lines in their respective organs. The goal of this study was to test the hypothesis that the LM and BoM lines exhibit differences in glucose and glutamine …

Exploring The Role Of Ccdc141 In Zebrafish Heart Development, Luci Strong

Honors Theses

Zebrafish are a good model organism in which to identify genes important for heart development because most human genes have a zebrafish ortholog and genes in zebrafish are relatively simple to modify. ccdc141 is a gene with unknown function, which we originally found to be highly expressed in cardiac cells in mouse embryos. In this project, we are seeking to determine the function of ccdc141 using zebrafish. To perform this experiment, we are targeting ccdc141 for mutation using CRISPR/Cas9. In this project we have analyzed ccdc141 to determine regions of conservation, designed CRISPR guides to target those regions (exon 2 …

Evaluation Of The Bax-Vdac Interaction And Their Influence On Apoptosis In Drosophila Melanogaster, Frances Marie Gatlin

Honors Theses

Apoptosis, also known as programmed cell death, is a cellular process used for development or for when cells undergo injury or stress. The Bcl2 family of proteins includes both pro-apoptotic and anti-apoptotic proteins that control the intrinsic pathway of apoptosis. Understanding the mechanisms and influence these proteins have on apoptosis is an important area of research focused on in Dr. Jones’s lab. Evidence shows a homology amongst the Bcl2 family of proteins at the BH3 domain. Dr. Jekabsons' lab has found a potential homology amongst VDAC 1-3 and the Bcl2 family at the BH3 domain.

Specifically, our lab is using …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr

Honors Theses

Antioxidants are well-known for their various health benefits. They are able to protect cells from being damaged by free radicals that are produced by vital biochemical processes. It has long been known that antioxidants are important in our everyday health, but their potential as disease preventers and potential therapeutic agents is a relatively new field of study. Resveratrol, a natural polyphenol and well-known antioxidant, is found in plants, fruits, and products derived from them, like red wine. Resveratrol has been shown to have various properties, including antiaging, anti-aggregation of platelets, anti-inflammatory, and anticancer activities. Because of their many health benefits, …

Development Of An Auto-Bioluminescent Lung Cell Line For Evaluation Of In Vitro Effects Of E-Cigarette Compounds On Normal Cell Proliferation, Olivia Morrison

Honors Theses

The effects of smoking have long been studied; however, with the rise of electronic cigarettes there is a growing interest in the effects of this smoking substitute. Marketed as a safer alternative to tobacco cigarettes, the popularity of electronic cigarette (e-cigarette) use has dramatically increased. This has demanded regulatory methods to be put into effect, however, scientific study is only beginning on the new fad to determine the impacts of its use on the human body. The present study aims to examine the biological effects of lung cell exposure to tobacco alkaloids found in electronic cigarette filling solutions. We hypothesize …

Evaluating Biogenesis Of 5’-Tailed Mirtrons, Jonathan D. Hoover

Honors Theses

MicroRNAs are 22 nucleotide, non-coding RNAs that serve as substrates for Argonaute proteins to induce RNA interference pathways. Intron-derived miRNA precursors called “mirtrons” have been identified and classified primarily through deep sequencing methods. Unlike most miRNAs, mirtrons are derived from splicing events and also exhibit high levels of post-transcriptional nucleotide addition to hairpin precursors. Most relevant among these modifications is 3’ uridylation as it inhibits mirtron biogenesis in multiple model systems. Mirtrons may also possess additional nucleotides adjacent to the pre-miRNA hairpin at the 3’ and/or 5’ ends. These nucleotide “tails” are removed prior to Dicer cleaving the hairpin. In …

Investigating Roles For Rna Turnover Processes In Cell Signaling Through Drosophila Melanogaster Genetic Mosaics, Sudiksha Rathan Kumar

Honors Theses

The process of cell signaling is vital in organisms for proper development as it determines the fate and function of cells. This process is highly regulated by myriad interactions between signaling pathway components and gene expression mechanisms. RNA turnover is a type of RNA processing that degrades RNA. It plays an essential role in homeostasis and environmental changes; however, its influence on signaling pathways is currently unknown. In the present study, the effect of RNA turnover processes on cell signaling was analyzed using the genetic mosaics in Drosophila melanogaster. Fly mosaics were created by breeding RNAi lines targeting cellular …

Mouse Embryonic Stem Cells Are Sensitive To The Cytotoxicity Of Nitric Oxide: Biological Implications For Early Embryogenesis, Mckenzie C. Hargis

Honors Theses

The early embryo, before implantation, is at a very vulnerable stage in development where it faces various inflammatory cytokines throughout the implantation process. In this stage, the cells in the blastocyst, the preimplantation stage embryo, must proliferate rapidly for tissue formation. However, it is known that inflammatory cytokines can inhibit cell proliferation. Previous studies have shown that embryonic stem cells (mESCs), the major cell component in the blastocyst, are unresponsive to treatments of tumor necrosis factor ⍺ (TNF⍺) and interferon 𝛾 (IFN𝛾), two inflammatory cytokines involved in the implantation process. Treatment of mESC-differentiated fibroblasts (mESC-FBs) with TNF⍺ and IFN𝛾 in …

Developing A New Water-Soluble Porphyrin As A Potential Photodynamic Cancer Therapy Agent, Catherine Shirley

Honors Theses

Photodynamic cancer therapy (PDT) is a type of treatment involving the use of light in conjunction with a photosensitive agent- a chemical or series of chemicals designed for activation when exposed to light. This research project investigated the synthesis and identification of the novel photosensitive agent, H2TPP-Pro-OH. To create the water-soluble porphyrin, (S)-(+)-prolinol was reacted with the tetra-carboxyl porphyrin, H2TPPC, to form the final H2TPP-Pro-OH product. This compound was then purified using syringe filtration and column chromatography, and subsequently characterized using infrared (IR), nuclear magnetic resonance (NMR), and Ultraviolet-visible (UV-vis) spectroscopies, as well as High Performance Liquid Chromatography (HPLC). Finally, …

Preparation And Cytotoxicity Of Novel Carbon Nano-Onion Materials, Cammie York

Honors Theses

The applications of carbon nanomaterials (CNM), including graphene and its derivatives such as carbon nanotubes (CNTs) in nanomedicine is well established. These nanomaterials have been widely used as theranostic delivery systems with the potential to deliver bioactive agents and simultaneously detect selectively diseased tissues. A rather underexplored CNM for biomedical imaging and theranostics delivery are carbon nano-onions (CNOs). CNOs are carbon-based nanomaterials that can potentially be used in cancer therapy when they are functionalized. Recent studies on cellular fate of different CNMs, including CNOs, have demonstrated that the surface composition is critical for the in vivo application of these CNM. …

Development And Validation Of Gene Delivery Methods For ​Crassostrea Virginica, Adrienne N. Tracy

Honors Theses

The Eastern oyster (Crassostrea virginica) is an important part of the East Coastal USA economy because aquaculture creates jobs. Sadly, the oysters are under constant threat due to increasing pollution, red tides, and diseases. Bivalves, and oysters in particular, are also becoming potential model organisms in medical research. With the sequencing of the oyster genome, scientists are focusing on deciphering the function of the predicted genes. However, the limited number of molecular and cellular tools available makes functional annotation of the genome challenging. A consistent, replicable gene delivery system needs to be developed to assess gene function and understand the …