Biochemistry Commons^™

Investigating The Ability Of Presequences To Influence Mitochondrial Protein Import, Youmian Yan

WUSM Theses and Dissertations – All Programs

Mitochondria are essential organelles housing over 1000 proteins, 99% of which are nuclear-encoded and synthesized in the cytosol. Most mitochondrial proteins are targeted by a positively charged sequence called the presequence, which lacks a common sequence motif and is poorly conserved across evolution. Accumulating evidence suggests that presequences encode meaningful information that influences mitochondrial protein uptake. For instance, multiple stress response models propose that stress sensing proteins contain “weak” presequences which allows them to monitor mitochondrial health. However, there is a lack of systematic examination about how presequences influence import kinetics and what constitutes presequence strength. These gaps in knowledge …

Sec-Saxs And Sans Analyses Of The Talin•Vinculin Complex, Gilbert Reyes

Dissertations, Theses, and Capstone Projects

Focal adhesions (FA) are integrin-based cell-matrix adhesion sites composed of adaptor proteins that facilitate the generation of traction forces important for biological functions such as cell migration, embryo development, wound healing, tissue organization and stability, and immune responses. Mature FA are observed when both autoinhibited multi-domain scaffolding protein talin and membrane-cytoskeletal protein vinculin are activated and interact thus promoting the assembly and function of FA. While research has resolved truncated sections of autoinhibited talin and recruitment of vinculin due to mechanotransduction that exposes cryptic vinculin binding sites (VBS), little is known about the global modifications of full length talin in …

Analysis Of Diterpenoid Alkaloids From American Aconitum Using Lc-Ms Metabolomic Methods, Yi Zhao

Dissertations, Theses, and Capstone Projects

Analysis of Diterpenoid Alkaloids from American Aconitum Using LC-MS Metabolomic Methods

by

Yi Zhao

Advisor: Edward J. Kennelly

Aconitum plants have been used as a traditional medicine in Asian countries for millennia to treat pain, rheumatism, syncope, fever, and other conditions. These therapeutic effects are mainly due to the bioactive diterpenoid alkaloids accumulated in the roots. Comparing with the large records and studies of Asian Aconitum and their medicinal use and the broad bioactive compounds, American Aconitum has been rarely investigated, not to mention how American Aconitum has been used medicinally. Based on previous phylogenetic and chemotaxonomic studies of Aconitum …

The Role Of External Factors In Shaping Carbohydrate Conformational Landscapes, Murat Yaman

Dissertations, Theses, and Capstone Projects

Carbohydrates (glycans) are among the most structurally diverse biomolecules and participate in a wide range of biological processes, including molecular recognition, cell adhesion, immune response, host-pathogen interactions, and cellular signaling. Their biological functions are governed by a complex interplay between sequence, stereochemistry, conformational flexibility, and environmental factors. However, the structural heterogeneity and dynamic nature of glycans present significant challenges for both experimental characterization and theoretical modeling. In particular, the relationships between glycan structure, conformational dynamics, and the resulting potential energy surfaces remain incomplete.

This dissertation investigates how external factors modulate the potential energy surfaces of carbohydrates through a combination of …

Riluzole As A Dual-Targeted Radiosensitizer For Osteosarcoma: Targeting Tumor Cells And Angiogenic Vasculature To Enhance Single High-Dose Radiotherapy Efficacy, Pooja P. Rao

Dissertations, Theses, and Capstone Projects

Osteosarcoma (OS), the most common primary bone malignancy of children and young adults, is intrinsically radioresistant, and outcomes for patients with unresectable or metastatic disease have not improved in over four decades. Single-dose radiation therapy (SDRT) is a potent modality against radioresistant, highly vascularized sarcomas, but its application in OS is constrained by dose-dependent normal tissue toxicity. Radiosensitizers achieving tumor control at lower doses therefore offer a direct route to widening the therapeutic window. Critically, OS radioresistance is not tumor-cell-autonomous. It emerges from two coordinated compartments: aberrant DNA repair and antioxidant capacity intrinsic to the tumor cell, and a radioprotective, …

Synthesis, Utilization And Biological Evaluation Of Β-Hairpin Peptides As Inhibitors Of Immune Checkpoints, Sarah Naylon

Electronic Theses and Dissertations

Peptide therapeutics have emerged as promising alternatives to monoclonal antibodies because of their smaller size, improved tissue penetration, and synthetic versatility. Yet their broader application is often limited by poor structural stability, rapid clearance, and reduced target residence times. This dissertation describes the design, synthesis, structural characterization, and biological evaluation of β-hairpin peptides as inhibitors of immune checkpoints and as peptide vaccine scaffolds while developing strategies to overcome these limitations. At first a series of antibody-derived β-hairpin peptides (mimics of complementary determining region heavy-chain 3: CDR-H3s) as covalent inhibitors of the PD-1/PD-L1 immune checkpoint were investigated. Electrophilic warheads were incorporated …

Towards The Synthesis Of Dragonamide E And Analogs Thereof, Dante Glover

Chemistry Theses

Leishmaniasis is a disease caused by a parasite spread through the female sand fly. It is categorized as a Neglected Tropical Disease and can cause very severe symptoms, even death, if left untreated. Symptoms include skin lesions that can cause permanent scarring, and mucosal membrane infections that can cause facial deformities. More aggressive forms of leishmaniasis can lead to infections of internal organs like the liver and/or spleen and can lead to death. Drug resistance of these parasites has rendered treatment limited and the side effects of which can be harmful as well.

Scientists looking towards new treatments for tropical …

Effects Of Variable Light On Sexual Competition In Kelp Species, Jaycee Lanza

Master's Theses

As foundation species, kelps significantly influence the structure and composition of their surrounding habitat by modifying environmental conditions, including light levels, currents, nutrient availability, sedimentation, and seawater chemistry. Light, in particular, is a critical resource that varies greatly within kelp forests, affecting kelp reproductive processes such as gametogenesis, fertilization, and recruitment, which are vital to population persistence. Biological factors, such as density-dependent competition for resources and sexual competition with other kelps, can also affect such processes. To understand how environmental variables influence kelp populations, it is crucial to recognize their combined effects. This study investigated the impacts of light levels …

Histone Deacetylases In Kidney Injury: Distribution, Injury-Specific Regulation, And Fibroblast Hdac1 Function, Huy Nguyen

ETDs from 2020-2029

Acute kidney injury (AKI) is increasingly recognized as a major contributor to the development of chronic kidney disease (CKD) through maladaptive repair and interstitial fibrosis. Epigenetic regulation has emerged as a critical factor of kidney injury responses, however the injury-specific and cell-type specific roles of histone deacetylases (HDACs) remain poorly defined. This dissertation investigates the regulation and functional significance of HDACs in kidney injury, with a particular focus on fibroblast HDAC1 as a mediator of interstitial fibrosis development following AKI. In my cisplatin-induced AKI model, a single dose of cisplatin caused a significant decline in kidney function in both male …

Elucidating The Mechanisms Of Complex Flavoprotein Dehydrogenases, Tyler Alt

Dissertations

Flavins are ubiquitous redox active cofactors that can catalyze electron transfer between substrates. They offer the advantage of being able to stabilize a range of oxidation and protonation states, as well being amenable to covalent modification, which can further alter their activity. As such, the scope of reactions catalyzed by flavoproteins is broad and flavin has implications in a range of biological processes. The two predominant forms of flavin that serve as redox active cofactors are flavin adenine mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are functionally homologous. A major complication of studying flavoprotein dehydrogenases, and one that has …

Synthesis And Characterization Of Organometallic Polymers And Their Cytotoxicity Towards Human Cancer Cell Lines, Paul Peter Slawek

Electronic Theses and Dissertations

This research aimed to synthesize organometallic polymers from dialkyl (methyl, ethyl, butyl, cyclohexyl, and octyl) and diaryl (phenyl) tin dichlorides and three organic monomers, dipicolinic acid (DPA), chloramphenicol (CH), and isomannide (IS), using interfacial polymerization. Structure-activity relationships were investigated through physicochemical characterization (light-scattering photometry, proton NMR, and IR spectroscopy) and cytotoxicity was evaluated against six human cancer cell lines (AsPC-1, PANC-1, MCF-7, MDA-MB-231, HT-29, PC-3), with cisplatin serving as the reference standard.

Five DPA/tin polymers were synthesized, with IC₅₀ values in the range of 0.60–0.71 μg/mL. Their cytotoxicity was significantly lower than that of cisplatin (0.0023-0.044 μg/mL), suggesting that …

Synthesis And Characterization Of Synergistic Bioactive– Organometallic Condensation Polymers, Francesca Isabel Mosca

Electronic Theses and Dissertations

This research focuses on the synthesis and structural characterization of polymers with anticipated anticancer and antiviral properties by combining metal-containing Lewis acids, organotin dichlorides (R2SnCl2), Group 4 metallocene dichlorides (Cp2TiCl2, Cp2ZrCl2 and Cp2HfCl2), and triphenyl Group 15 metal dichlorides (Ph3AsCl2, Ph3SbCl2 and Ph3BiCl2), with biologically active Lewis bases, lamivudine, a synthetic nucleoside, and camphoric acid, a dicarboxylic acid, to achieve synergistic effect.

Five classes of polymers were synthesized using interfacial polymerization: lamivudine and organotin dichlorides, lamivudine and Group 4 metallocene dichlorides, camphoric acid and triphenyl Group 15 metal dichlorides, camphoric acid and organotin dichlorides, and camphoric acid and Group 4 …

Immunomodulatory And Signaling Molecules From Plant-Associated Bacteria: Toll-Like Receptor 4 Agonist Adjuvants And Diketopiperazine-Mediated Communication, Marian Romaine

Dissertations, Theses, and Capstone Projects

Medicinal plants and their associated microbiomes constitute a rich source of bioactive natural products with applications in immunotherapy and microbial ecology. Herbal formulations have long been valued for safe immune enhancement, while bacterial signaling molecules govern community behaviors critical to pathogenesis, symbiosis, and environmental processes. Bacterial lipopolysaccharides (LPS) from plant-associated Gram-negative bacteria have emerged as potent TLR4 agonists, yet their endotoxic potential limits direct use, and diketopiperazines (DKPs) serve as versatile quorum-sensing mediators capable of modulating biofilms in mixed microbial systems.

The work in this thesis comprises two independent but complementary research strands. The first strand pursued the engineering of …

Identifying Textual Predictors Of Early Termination In Clinical Trials In Medicine: An Explainable Machine-Learning Study, Rohan Ramnarain

Dissertations, Theses, and Capstone Projects

About one in five clinical trials in medicine ends early, wasting valuable resources and reducing the evidence available for developing life-saving medical treatments. This project uses a method called Trial2Vec, which is a self-supervised machine-learning method that converts clinical trial documents into dense numerical representations that capture their key design and clinical characteristics, to turn each proposed clinical trial’s written protocol into a compact numerical profile (a process referred to as embedding). These profiles are then paired with a predictive machine learning models to identify the words and phrases in the trial documents that can signal a higher risk of …

In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel

Biological Sciences Theses and Dissertations

One of the major causes of treatment failure in aggressive cancers is multidrug resistance (MDR), which is linked to the overexpression of membrane efflux proteins that export chemotherapeutics from cancer cells. This mechanism prevents chemotherapeutic drugs from reaching cytotoxic concentrations intracellularly, allowing the cancer to survive. Two primary mediators of this mechanism are P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). P-gp and BCRP are transmembrane ATP-binding cassette (ABC) transporters that are frequently overexpressed in MDR cancers. They utilize the binding and hydrolysis of ATP to transport a diverse range of amphipathic molecules of varying size (Schinkel and Jonker, 2003), …

Microtubules In Breast Cancer: Exploring The Α/Β-Tubulin Toggle Switch And Its Implications In Human Breast Cancer, Annemarie Ianos

Student Theses and Dissertations

Microtubules, composed of a/b-tubulin heterodimers, play a central role in breast cancer tumor growth by polymerizing, leading to metastasis and depolymerizing, contributing to proliferation. Human enzymes protein kinase Ca (PKC-a) and cyclin-dependent kinase 1 (Cdk-1) mediate phosphorylation at sites a:Ser165 and b:Ser172, respectively, influencing the growth of microtubules. It is possible that alternating phosphorylation at these sites contribute to an a/b-tubulin “toggle switch” that mediates microtubule instability and tumor growth.

The project investigates the influence of the toggle switch model on microtubule stability by determining the impact of mutants (a:S165D, a:S165N, a:S165S_P, b:S172S_P and a:S165S_P/b:S172S …

Computational Design Of Peptides And Proteins Through Machine Learning Approaches, Emily J. Hendrix

Chemistry and Chemical Biology ETDs

Advancements in machine learning have emerged as a pivotal tool in computational biochemistry, offering new advancements to address challenges in protein structure and function. However, current machine-learning approaches offer limited insight in understanding protein dynamics. The purpose of this work is to combine traditional physics-based computational tools, such as molecular dynamics and coarse-grained simulations, with recently developed AI-driven computational tools to bridge gaps and advance the understanding of proteins in both structural and dynamic aspects. I investigated several approaches such as (i) traditional physics-based methods to study protein conformation and ensembles; (ii) identifying a peptide inhibitor for the PICK1 PDZ …

Virus-Like Particle Peptoid Conjugate As A Triple-Negative Breast Cancer Targeting Delivery System, Ricky Zhu

Chemistry Theses

Triple-negative breast cancer (TNBC), an aggressive form of breast cancer, characterized by its lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2) poses a therapeutic challenge as common treatment options are rendered ineffective. Here is a strategy to develop a drug delivery system utilizing poly-glycinated LC129 8, a TNBC targeting peptoid, covalently attached to HK97 virus-like particles (VLP) containing a C-terminal LPETG sequence via a sortase mediated reaction. Using the properties of the cage-like structure of VLPs and the TNBC specificity of the LC129-8, high doses of chemotherapy can be efficiently loaded into the …

Skin Of Frog And Scale Of Dragon: Nutritional Cues, Life Cycle Kinetics, And Secretome Dynamics In Batrachochytrium Dendrobatidis, Naomi C. Okada

UNLV Theses, Dissertations, Professional Papers, and Capstones

Nearly 50% of amphibian species are at risk of extinction, making them the most threatened group of vertebrates on the planet. A major driver of these declines is the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd), which causes the fatal skin disease chytridiomycosis. Since its discovery in the late 1990s, Bd has been directly implicated in the extinction of 90 species of amphibians and the declines of hundreds more. Despite this devastating ecological impact, relatively little is known about its basic cellular biology.

Bd has a multi-stage asexual life cycle consisting of a motile and infectious zoospore, which encysts (into a …

Bax Activation Through The N-Terminal Bh3-Like Domains Of Vdac1 And Vdac2, Autumn A. Peters

Honors Theses

Voltage-dependent anion channels (VDACs) are central to mitochondrial function by mediating metabolite diffusion across the mitochondrial outer membrane (MOM). Two isoforms­­­­­­­­­­­,­­­­­­­­­­­­­­­­­­­­­­­­­­­­ VDACs 1 and 2, are also implicated in apoptosis based on interactions with Bcl-2 family proteins that control this process, including Bax and Bcl-xL. Activation of the pro-apoptotic protein Bax by interaction with ‘BH3-only’ proteins, such as Bim or Bid, induces MOM permeabilization to signal apoptosis, yet accumulating evidence indicates VDACs 1 and 2 may also affect Bax. We discovered that the VDAC N-terminal domains contain high sequence similarity to the conserved BH3 domains within Bcl-2 family members that …

Functionalized Nanodiamonds As Binding Platforms For Single-Stranded Dna, Mallory A. Chapman

Honors Theses

Nanodiamonds (NDs) offer a promising platform for biomolecular applications due to their stability, biocompatibility, and three-dimensional structure. This study focused on developing a nanodiamond–DNA complex in which streptavidin-functionalized NDs would form a protective shell around biotinylated single-stranded DNA (ssDNA), creating a core–shell system like an “M&M” candy with DNA at the center and a protective coating on the outside. DNA has many uses in nanotechnology, including DNA origami, nanomachines, and drug delivery systems, but its degradation limits its practical use, making protective strategies essential.

ND–DNA conjugates were prepared using biotin–streptavidin interactions and analyzed using gel electrophoresis. Initial separation on agarose …

Biochemical Characterization Of Luciferase In Omphalotus Olearius, James H. Martin

Honors Theses

The overall goal of this thesis was to investigate the genetic basis of bioluminescence in Omphalotus olearius, a bioluminescent mushroom. The project initially focused on growing fungal cultures under controlled laboratory conditions and using molecular techniques such as DNA extraction, PCR, and gel electrophoresis to identify the organism and isolate the gene responsible for light production. The main objective was to insert this gene into a bacterial system to confirm its function through observable bioluminescence. However, repeated difficulties in maintaining viable fungal cultures and errors in molecular procedures resulted in inconclusive results, preventing successful gene identification. Due to these …

Isolation, Purification, And Characterization Of Α-Galactosidase From Watermelon (Citrullus Lanatus), Christopher Henley Jr.

Chemistry & Biochemistry Undergraduate Honors Theses

The enzyme α-galactosidase is a type of glycosidase that removes galactose sugar units from larger molecules in cells. Compounds that inhibit glycosidases have been useful for understanding the structure and function of the enzymes they inhibit, and some have been used to treat certain diseases. Using inhibitors of α-galactosidase to study its characteristics and mechanisms may provide insights into its role in disease and its general utility. Advances in fields such as agriculture, sustainable fuels, and biomedicine may be facilitated by inhibition studies of α-galactosidase, but the current library of known inhibitors is relatively lacking. Obtaining α-galactosidase enzymes from chemical …

Shark Immunology And Its Biomedical Potential: Evolution, Innovation, And The Imperative Of Conservation, Reesha Bhagat

Undergraduate Honors Thesis Collection

This review aims to shed light on a significant ecological deficit and its implications for the future of science and medicine. Sharks possess a uniquely adaptive, cancer-resistant, and evolutionarily refined immune system with transformative biomedical potential, making their conservation a scientific and medical imperative. We are losing something medically irreplaceable, and we don’t even fully understand it yet. Shark conservation is a pressing scientific imperative because sharks are ecologically essential and represent an irreplaceable biomedical resource.

Acute Effects Of The Psychoactive Pollutant Fluoxetine On The Antipredator Behavior Of The Gulf Killifish (Fundulus Grandis), Semyra Reus

Honors Theses

Pharmaceutical contaminants are increasingly prevalent in aquatic environments, yet their sublethal effects on ecologically relevant behaviors remain poorly understood, particularly in estuarine systems. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are of particular concern due to the conserved role of serotonin in regulating behavior across vertebrates. Here, we investigated how acute exposure to environmentally relevant concentrations of fluoxetine influences anti-predator behavior in Gulf killifish (Fundulus grandis), a key estuarine fish commonly found in saltmarsh habitats. Killifish were exposed to control (0 ng/L), low (17.8 ng/L), and high (596 ng/L) fluoxetine concentrations and subsequently tested in the presence …

Ethanol State-Dependent Learning In The Honey Bee (Apis Mellifera), Ethan Neil Govea

Theses and Dissertations

Ethanol disrupts neural circuits involved in addiction and withdrawal, yet the molecular mechanisms underlying these effects remain poorly understood. One possibility is that ethanol alters an animal’s perceptual or internal state, causing a stimulus learned while intoxicated to be processed differently when the animal is sober. This study examined how ethanol exposure affects odor learning, recall, and discrimination in honey bees, a useful model because of their robust olfactory learning and experimentally accessible neural systems. Bees were differentially conditioned with appetitive reward (sucrose) during hexanol exposure and aversive stimulus (quinine) during decanol exposure. To assess olfactory processing and state dependency, …

Identification Of Peptides For A Muc13 Cancer Vaccine, Abigail Olivia Gomez

Theses and Dissertations

Mucin 13 (MUC13) is a transmembrane glycoprotein that is frequently overexpressed in epithelial cancers. Its extracellular domains and cytoplasmic signaling potential contribute to disrupted cell adhesion, increased invasion, and cancer-promoting pathways, making MUC13 a promising target for immunotherapy. This project used an in-silico approach to identify MUC13-derived peptides predicted to bind HLA class I molecules and support CD8+ T cell-mediated immune responses. Bioinformatics tools were used to screen candidate epitopes for HLA binding affinity, antigenicity, toxicity, IFN-γ-inducing potential, and population coverage, allowing rational prioritization of peptide candidates for experimentation. Selected peptides were evaluated in THP-1-derived macrophages using RT-PCR, Western blotting, …

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Mechanisms Of Bacterial Glucokinase Inactivation Through Site-Specific Lysine Modification And Chemical Inhibition, Joseph Robert Will Andrews

Graduate Theses and Dissertations

Glycolysis and related metabolic pathways are controlled by various post-translational modifications (PTMs) that affect enzyme activity and metabolic flow. In E. coli, glucokinase (GLK) sits at the crossroads of glycolysis and the pentose phosphate pathway and carries out the first committed step of glycolysis: ATP-dependent phosphorylation of glucose. While it's known that glucose binding causes GLK to close its domains, how phosphate binding, lysine modification, and small-molecule inhibitors regulate GLK's shape and function is still not fully understood. Here, I combine structural biochemistry and enzymology to figure out how phosphate binding, specific mutations, and chemical inhibitors affect E. coli GLK. …

A Novel Method Of Protein Purification Using Hedgehog Proteins As An Inducible, Self-Cleaving Tag, Antonia Kladias

Undergraduate Honors Theses

Because removing extraneous purification tag sequences from native proteins can be challenging and costly, there is demand for simple all-in-one techniques that directly furnish a tagless, functional protein-of-interest (POI). Current tagless purification systems are based on intein biochemistry; however, intein-based purification requires expensive, specialized resins and the POI often must be fused to the intein’s C-terminus. In this thesis, I present a novel approach for tagless POI purification in which the Drosophila melanogaster hedgehog protein catalytic domain (HhC) is repurposed as a small-molecule inducible, self-cleaving element dubbed Gtag. With Gtag, the POI is fused to the N-terminus of HhC/Gtag with …