Biochemistry, Biophysics, and Structural Biology Commons^™

Nanostructured Materials For Biomedical Applications, Silverio Lopez

Theses and Dissertations

Nanotechnology has been used in an increasing number of applications in biochemistry and molecular biology. Compared to bulk materials, nanoscale materials offer a variety of advantages in applications due to an increased surface-to-volume ratio of the reactants. The unique properties of nanostructured materials and their properties such as stability, reactivity, magnetic response, pressure discharge performance and biocompatibility depend on particle size and shape. This work focuses on a nanoenergetic material composed of Aluminum (Al), Copper II oxide (CuO), and Iodine (I) pentoxide (I2O5), and the biomedical application of nanoscale dextran-coated magnetite (Fe3O4), which was produced using microfluidics to tune particle …

Assessing The Effects Of Levonorgestrel (Lng) On Neural Differentiation In The Developing Hypothalamus Using The Zebrafish (Danio Rerio) As A Model, Gabriella Hinojosa

Theses and Dissertations

Neurogenesis is a critical component of fetal neurodevelopment consisting of: migration, proliferation and differentiation. Health concerns from anxiety to reproductive issues have been linked to alterations of neurogenesis processes. Endocrine disrupting chemicals (EDCs) can mimic hormones vital to this process, potentially adversely affecting the susceptible fetal brain. One EDC, Levonorgestrel (LNG), is a testosterone-like progestin used in birth control methods that has a high bioavailability and long half-life. Using zebrafish embryos as a model, this lab previously discovered that an environmentally relevant LNG dose (5 ng/L) significantly increased anxiety behaviors. The hypothalamus is responsible for the development …

Exploring Dna Compaction Via Bacillus Subtilis Parb Protein By Single Molecule Investigation, Miranda L. Molina

Theses and Dissertations

Faithful chromosome segregation involves ParB, a DNA-binding and compacting protein that specifically recognizes parS DNA sites near the replication origin. ParB spreads 10-20 kb from parS sites, which recruitments additional ParB molecules to neighboring DNA, forming higher-order nucleoprotein complexes. ParB is also a novel CTPase enzyme and hydrolyses CTP to self-dimerization and create a clamp that slides along DNA. To understand the roles of CTP in Bacillus subtilis ParB (BsParB), we purified wild type ParB (BsParB (WT)) and recombinant ParB (BsParB(R80A)) mutant. BsParB(R80A) was known to prevent CTP binding and not compact DNA. Proteins N- and C-terminally appended with a …

Structures And Regulations Of Translation Initiation Factors In Pseudomonas Aeruginosa Protein Biosynthesis To Develop New Potential Antimicrobial Agents, Nicolette Valdez

Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative, multidrug resistant bacterium that has been recognized as the prominent cause of nosocomial infections. Untreated acute and chronic infections associated with P. aeruginosa can develop into other diseases such as pneumonia, otitis externa, and osteomyelitis. P. aeruginosa infections commonly affect immunocompromised individuals such as cystic fibrosis, cancer, and burn patients. The misuse and overuse of antibiotics has contributed to the increased antibiotic resistance in P. aeruginosa and thus has led to an unmet need for discovery of novel antibiotic candidates. Protein biosynthesis is an essential metabolic process occurring in all bacteria and a validated target …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair

Dissertations and Theses (Open Access)

KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …

Tissue-Specific Matrix Control Of Cell Cohesion And Migration Signaling Complexes, Tristen Tellman

Dissertations and Theses (Open Access)

The extracellular matrix (ECM) is a complex, interconnected network of three major constituents: collagens, glycoproteins, and proteoglycans, along with their enzyme modifiers. Within this network and beyond the structural role, each ECM molecule contributes a context-specific signal that influences cellular fate and behavior. Among these behaviors, cellular migration provides an essential function in developing tissues, wound healing, and cancer cell metastasis. Using two glandular organs, the normal salivary gland and the cancerous prostate, this dissertation describes the tissue-specific composition of two ECM signaling complexes (type I hemidesmosomes and the perlecan-semaphorin 3A-plexin A1-neuropilin-1 (PSPN) complex) and translates this knowledge into viable …

Plant Homeodomain Finger Protein 20 (Phf20) And Its Homolog Phf20 Like 1 (Phf20l1) Define Two Distinct Non-Specific Lethal (Nsl) Complexes, Hieu Van, Hieu T. Van

Dissertations and Theses (Open Access)

Plant Homeodomain Finger Protein 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known subunits of the Non-Specific Lethal (NSL) complex, which acetylates lysine residues on histone H4 and regulates gene expression. The current model assumes that PHF20 and PHF20L1 are present together in the NSL complex, although it has never been tested. Performing extensive biochemical analysis, we observed that PHF20 and PHF20L1 were exclusively and independently associated with the NSL complex. Our protein domain analysis showed that the C-termini of PHF20 and PHF20L1 are crucial for their interactions with the respective complexes. Furthermore, enrichment sites of PHF20 and …

Utah Tick Surveillance An Animated Public Service Announcement, Keith Wilson

Undergraduate Honors Capstone Projects

As the United States’ population grows, we develop more land into housing and recreate farther into wilderness areas, consequentially encountering ticks with increasing frequency. As the climate continues to change, tick population distributions are also changing, influencing our population’s exposure to tick-borne diseases. Lyme disease, a tick-borne disease named after Lyme, Connecticut, is one of the fastest growing emerging diseases in North America, and the most prevalent vector-borne infection in the United States. There are two species of tick in North America, Ixodes scapularis and Ixodes pacificus, known to be carriers of the causative agent of Lyme disease, a …

Floating Treatment Wetlands For Brackish Waters: Plant Selection And Nutrient Uptake Potential., Andrea Landaverde

All Theses

Brackish water bodies in coastal regions provide critical ecosystem services that support human and environmental health. Anthropogenic activities such as agricultural and industrial activities, construction, urban settlements, and tourism contribute to increased inputs of nitrogen (N) and phosphorus (P) in brackish coastal ecosystems. Excess nutrients can lead to impaired water quality and affect marine organisms. Floating treatment wetlands (FTWs) are a vegetated-base technology used to remove contaminants from water column, that has been mainly studied and applied in freshwater systems. Application of FTWs in brackish systems requires further investigation, as high salinity in brackish waters could result in toxicity to …

Optimization Of Modular, Long-Range, Ultra-Fast Optical Tweezers With Fluorescence Capabilities For Single-Molecule And Single-Cell Based Biophysical Measurements, Subash C. Godar

All Dissertations

An Optical tweezer is a tightly focused laser beam that applies and senses precise and localized optical force to a dielectric microsphere and offers a unique and effective tool for manipulating the single cell or cell components, including nucleotides and dynein motor proteins. Here, I used highly stabilized optomechanical components and ultra-sensitive detection modules to significantly improve the measurement capabilities over a wide range of temporal and spatial scales. I combined the optical tweezer-based force spectroscopy technique with fluorescence microscopy to develop an integrated high-resolution force-fluorescence system capable of measuring displacements at sub-nanometer, forces at sub-piconewton over a temporal range …

Preparation Of Proteins And Peptides From Heat-Stabilized Defatted Rice Bran Via Solid State Fermentation And Investigating For Skin Health, Ali A. Bisly

Graduate Theses and Dissertations

Heat-stabilized defatted rice bran (HDRB) is an abundant and inexpensive agro-industrial by-product of rice milling and rice oil extraction process. Furthermore, HDRB is a potential source of proteins. However, the direct protein extraction has low yield of protein due to the impact of heat stabilization and oil extraction process which made the HDRB proteins bound and interact with other components. This research is based on using solid-state fermentation (SSF), which is a natural and cost-effective approach to facilitate protein extraction from HDRB using Bacillus subtilis (natto) Takahashi as a microorganism.

Response surface methodology (RSM) analysis was used with Box-Behnken design …

Study Of Adaptive Radiation Effects On Sprint Performance In Anolis Ecomorphs, Alexander J. Bergeson

Honors Thesis

Anolis lizards have become model organisms for the study of adaptive radiation and convergent evolution due to repeated patterns of specialization that allow them to live in different environmental niches within the habitats they occur. As part of a suite of adaptations for living in specific habitats, many species have repeatedly evolved specific changes in anatomy and physiology that make them better able to perform and survive in their surroundings. These specialized forms are referred to as “ecomorphs” based on their preferred habitats and have been well documented among Caribbean anoles. Mainland species, on the other hand, are less studied. …

Characterization Of A Protein-Small Molecule Interaction Between Microtubules And Novel Ruthenium-Polypyridyl Complexes, Chloe Hutchison

Chemistry & Biochemistry Undergraduate Honors Theses

Microtubules are cytoskeletal filaments that play a role in essential functions within the cell such as cell motility, intracellular transport, structural support and chromosome segregation. Tubulin is a heterodimeric protein that exhibits GTP dependent polymerization and self- assembles into polar microtubule filaments. Microtubules are dynamic polymers corresponding to their role in separation of duplicated chromosomes during mitosis. As the polymers cycle through rounds of polymerization and depolymerization based on their nucleotide state, the chromosomes are pulled towards the poles in the mitotic cell. Their normal function and dynamics can be disrupted in highly proliferative cells that interrupt cell cycle progression …

Investigation Of The Binding Domain Interfaces Of The C-Terminus Of The Albino3 Insertase And The 43kda Chloroplast Signal Recognition Particle Subunit Via Single Molecule Förster Resonance Energy Transfer, Amanda Tomanek

Chemistry & Biochemistry Undergraduate Honors Theses

Fluorescent labeling is a technique used for visualizing functional groups contained in biomolecules by fluorescence imaging. This technique was used in this project to analyze post-translational targeting of light-harvesting chlorophyll-binding proteins (LHCP), which are the core complexes that harvest sunlight to drive photosynthetic electron transfer. This protein is synthesized in the cytosol and post-translationally targeted to the stroma of chloroplasts. CpSRP43 is a signal recognition particle (SRP) subunit unique to chloroplasts, which has been shown to interact with the stroma-soluble C-terminus of the thylakoid-bound Albino3 insertase (Alb3-Cterm). In the chloroplast stroma, targeting to thylakoids is performed via the cpSRP pathway …

Studying The Lysine Acetylation Of Aconitase Isozymes In E. Coli, Sara Ottinger

Chemistry & Biochemistry Undergraduate Honors Theses

The contents of this thesis have been modified from the publication “Araujo J, Ottinger S, Venkat S, Gan Q and Fan C (2022) Studying Acetylation of Aconitase Isozymes by Genetic Code Expansion. Front. Chem. 10:862483”. Though studies have found multiple lysine sites in which acetylation takes place in Escherichia Coli aconitase, acetylation’s effects on the enzyme’s activity have yet to be studied. Aconitase is the dehydratase-hydratase found in the citric acid and glyoxylate cycles responsible for the reversible isomerization of citrate to isocitrate via cis-aconitate intermediate. There are two isoforms of aconitase in E. coli: AcnA and AcnB. In …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

Severe Hypoxia Up-Regulates Gluconeogenesis In Daphnia, Morad C. Malek

Undergraduate Honors Theses

Hypoxia is a significant low oxygen state that has complex and diverse impacts on organisms. In aerobes, various adaptive responses to hypoxia are observed that vary depending on the level of oxygen depletion and previous adaptation, hence the continued attention to hypoxia as an important abiotic stressor. Adaptive responses to hypoxia are primarily governed by the hypoxia-inducible factors (HIFs), which activate downstream genetic pathways responsible for oxygen transport and metabolic plasticity. In aquatic habitats, oxygen availability can vary greatly over time and space. Therefore, aquatic organisms’ adaptation to hypoxia is likely pervasive, especially in genotypes originating from waterbodies prone to …

Vitamin D And Its In Vitro Therapeutic Action Mediated Through Vdr Rather Than Pdia3, Jaeden Pyburn

Undergraduate Honors Theses

Brain calcification is a common occurrence in the aging process, with >20% of individuals over the age of 65 showing hardened plaques in the basal ganglia. Loss of the vitamin D receptor (VDR) in transgenic mice leads to formation of calcified plaques in the basal ganglia and thalamus within the mice. Vitamin D signals through two known vitamin D responsive proteins, protein disulfide isomerase A3 (PDIA3) and VDR. In vitro, vitamin D has been demonstrated to suppress calcification in osteoblast-like cells. Here, we aim to elucidate which of either PDIA3 or VDR transduce vitamin D mediated suppression of calcification in …