Biochemistry Commons^™

Structural Analysis Of Pseudomonas Phage Dev Virion-Associated Rna Polymerase (Gp71), James Scherer

All ETDs from UAB

DEV is a Pseudomonas aeruginosa bacteriophage part of a newly reclassified genus called Schitoviridae. This group of bacteriophages is also referred to as “N4-like” phages, after the prototypical Escherichia coli phage N4, originally isolated from sewage water in 19661. N4, and other phages in the group, contain a large, virion-associated RNA polymerase (vRNAP). This vRNAP is vital to the proliferation of the phage, as it performs the transcription of the early gene products and potentially acts as a motor that helps eject the viral genome into the host bacteria. In DEV, the vRNAP is also known as gene product 71 …

Virulence Factors And Their Binding Partners: A Biochemical Study, Morgan E. Blake

All ETDs from UAB

Virulence factors are an important mechanism by which viruses combat the host immune system, therefore a thorough understanding of the workings of these proteins will be of significant value in prevention of disease associated with viral infections. In this dissertation we investigate the main virulence factors of two viruses, the Influenza A Virus (IAV) and SARS-CoV-2, and their interactions with host proteins, providing critical information for structure-based drug design. In chapter one we studied the nonstructural protein 1 (NS1) of IAV and its interaction with the 30-kda subunit of the cleavage and polyadenylation specificity factor (CPSF30) to inhibit host cell …

Structural And Functional Investigation Of The Influenza Nuclear Export Protein, Andrew James Staup

All ETDs from UAB

The influenza A nuclear export protein (NEP) is a multi-functional protein that mediates the export of progeny viral ribonucleoprotein (vRNP) complexes from the host nucleus, regulates the activity of the RNA-dependent RNA polymerase (RdRp), and is implicated in zoonosis. It is therefore critical to understand the mechanisms of NEP’s functions at the molecular level to inform its roles in the viral lifecycle and influenza zoonosis. In this dissertation, we report the structure of NEP in complex with the host nuclear export holo-complex as well as investigate the biophysical effects of the adaptive M16I mutation on NEP. We solved the cryo-electron …

Data From: Nek4 Suppresses Cell Proliferation In Bt20 Triple-Negative Breast Cancer Cells By Diminishing Expression Of Cell Cycle Genes, While Its Depletion Mitigates Proliferation In Other Cell Lines, Amanda Ashley

Chemistry & Biochemistry: Datasets

No abstract provided.

The Next Frontier In The Study Of Noncovalent Bonding: Transition Metals, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

As work continues unabated in the study of noncovalent bonding, particularly σ-hole bonds, new challenges have emerged as the participation of transition metals in interactions of this sort is fast becoming appreciated. While there are certain similarities with the halogen, chalcogen, etc, bonds, in which the main group elements participate, there are certain unique properties of these metal atoms that must be analyzed before a complete understanding can be attained. As one example, these atoms tend to act simultaneously as both electron donors and acceptors, a synergistic action that amplifies the overall bond strength. Ideas are expressed in this paper …

Analysis Of Antibody Affinity Maturation And Thermal Stability Of Proteins Using Photophysical Approaches, Claire Baxter

Dissertations

Engineered antibodies (Abs) have found applications in disparate fields such as enzyme catalysis and medicinal therapeutics because of their exquisite binding affinity and specificity. To engineer antibodies for these purposes, a firm understanding of the underlying mechanisms that control Ab affinity and specificity is needed, so these properties can be tightly controlled and adapted to the application at hand. My research characterized the binding site of the anti-fluorescein Ab 4-4-20 using an array of biophysical techniques and gives insight into the binding site interactions that give rise to both affinity and specificity. We utilized Fab fragments of the anti-fluorescein Ab …

Development Of Single Droplet Interface-Specific Sum Frequency Scattering Spectroscopy, Yi Rao

Funded Research Records

No abstract provided.

Root Exudates: The Rhizospheric Frontier For Advancing Sustainable Plant Protection, Muhammad Rahil Afzal, Misbah Naz, Youbo Yu, Lisha Yan, Peiyi Wang, Janaki Mohotti, Gefei Hao, Jing-Jiang Zhou, Zhou Chen, Libo Zhang, Qian Wang

Faculty Publications

Root exudates (REs), a diverse array of bioactive metabolites secreted by plant roots in response to environmental stimuli, serve as key mediators of rhizosphere ecology and plant defense responses, offering a promising avenue for sustainable pest management and eco-friendly plant protection. While earlier reviews primarily focus on root exudates in the context of general rhizosphere dynamics and plant-microbial interactions, critical knowledge gaps persist in REs-plant-pest tripartite interactions, the mechanistic basis of REs-mediated plant defense, and their practical integration with integrated pest management (IPM) frameworks. This review provides a synthesis of the latest literature on the biochemical diversity and functions of …

Impact Of Varied Dietary Macronutrient Ratios On The Nutrition Status Of Swiss Albino Mice, Hellen Kinyi, Charles Kato, Gertrude Kiwanuka

Biomedical Sciences, East Africa

The nutrition status of an organism depends on the balance between nutrient intake and utilization. Malnutrition results not only from inadequate caloric intake but also from imbalanced macronutrient ratios, which can affect aging, metabolism, and health. While many studies focus on individual nutrients, this study used purified, isocaloric diets with varying macronutrient ratios to assess dietary effects on nutrition markers in Swiss albino mice.

Mice were randomized into 6 dietary groups, each containing 6 males and 6 females housed separately. Each group received an isocaloric diet with different carbohydrate, protein, and lipid ratios for 15 weeks. Animal weight, body mass …

Single Nuclei Transcriptomics Reveals Cellular Diversity In Tsc Subependymal Giant Cell Astrocytomas, Jennie C. Holmberg, Vijay Shankar, Rachel A. Lyman, Trudy F.C. Mackay, David M. Feliciano

Publications

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign growths called hamartomas that are a significant cause of morbidity and mortality. Hamartomas are found along the neurocutaneous axis including along the brain’s ventricles near the boundaries of the striatum. They can be categorized by size and include small subependymal nodules (SENs) or larger subependymal giant cell astrocytomas (SEGAs). Here, we describe a quantitative analysis of SEGA cell identities based on single nuclei RNA sequencing. SEGAs contain several cell types. In contrast to unaffected samples, SEGAs have pronounced vasculature, more endothelial cells, increased perivascular macrophages, less myelination, and altered …

From Sequence To Allostery: How Amino Acid Differences Rewire Coupled Conformational Heterogeneity In The Ptp Enzyme Family, Shivani Sharma

Dissertations, Theses, and Capstone Projects

Protein Tyrosine Phosphatases (PTPs) are critical regulators of cellular signaling, and their activity is often modulated through allosteric mechanisms. Allostery is defined as a chemical or conformational change in one site of the protein due to a binding event at another site. Although several studies have investigated aspects of allostery in PTPs, the mechanistic foundations underlying allosteric regulation remain poorly understood. Despite a highly conserved catalytic domain across PTPs, regions with low or no conservation suggest potential "rewiring" of allosteric networks. This raises key questions about the universality versus individuality of allosteric mechanisms across the PTP family.

In this work, …

Mechanistic Insights Into The Neuroprotective Effects Of The Antidepressant Agomelatine In Alzheimer's Disease, Grace Terry

Dissertations, Theses, and Capstone Projects

Alzheimer’s Disease (AD) is a complex neurodegenerative disease that has limited treatment options and no cure. AD is characterized by robust pathology including extracellular amyloid beta plaques, intracellular neurofibrillary tangles, neuronal and synaptic loss, neuroinflammation, and brain atrophy. AD presents with cognitive decline and memory loss but only years after neuropathology has started to accumulate. This robust pathology has made AD difficult to treat and highlights the need for therapeutics that modulate multiple pathways. Agomelatine (AGO) was selected by a high-throughput machine learning drug repurposing algorithm by our collaborator Dr. Lie Xie (Hunter College Dept. of Comp. Sci.) as having …

Development And Implementation Of Novel Mass Spectrometric Methods For Metabolism Studies In Drug Discoveries, Huifang Yao

Dissertations

The field of drug discovery has evolved significantly over the past few decades, with a growing emphasis on understanding the metabolic pathways and biotransformation processes that influence the pharmacokinetics and pharmacodynamics of drug candidates. Novel mass spectrometric methods have emerged as powerful tools in this domain, facilitating the comprehensive analysis of metabolic profiles and enabling the identification of metabolites with implications for safety, efficacy, and overall drug development. However, challenges remain in quantifying metabolic flux—an essential aspect of understanding drug action—particularly due to the limitations of traditional isotope kinetic assays, which often involve lengthy sample preparation and the use of …

Role Of Nucleic Acids As Chaperones In Protein Folding, Zijue Huang

Electronic Theses and Dissertations

Many proteins have slow folding times in vitro that are physiologically untenable. To combat this challenge, ATP-dependent chaperonins are thought to possess the unique ability to catalyze protein folding. Performing quantitative model selection using protein folding and unfolding data, we here show that short nucleic acids containing Gquadruplex (G4) structure can also catalyze protein folding. Performing the experiments as a function of temperature demonstrates that the G4 reshapes the underlying driving forces of protein folding. To understand the structural basis of this catalytic activity, we introduce NMR method to solve the structures, at base-level resolution, of a multiconformer G4 with …

3d Bioprinting On Electrospun Nanofibrous Scaffolds To Fabricate Myocardial Patches, Muthu Parkkavi S

Theses and Dissertations

Tissue-engineered three-dimensional (3D) myocardial patches offer superior and innovative treatment strategy for myocardial infarction (MI). Among the various scaffold fabrication techniques, electrospinning and 3D bioprinting have received great attention due to their ability to recreate native cardiac tissue mimetic characteristics. Despite several advantages, electrospun nanofibers have limitations in cell delivery due to random cell seeding, while bioprinting faces challenges in creating hydrogel constructs with ideal mechanical properties capable of supporting cardiac contraction/relaxation cycle. Hence in this work, hybrid myocardial patches were developed by converging electrospinning and bioprinting techniques.

Electrospinning of PLCL:PEOz (B73, 7:3 blend of poly-L-lactide-co-ε-caprolactone (PLCL) and polyethyl oxazoline …

Empowering Science With The World's First High Accuracy And High Throughput Functional Assay, Christopher Giacoletto

UNLV Theses, Dissertations, Professional Papers, and Capstones

Understanding the functional consequences of genetic mutations remains a central challenge in modern biology, with far-reaching implications for human health and disease. While early systematic methods like alanine scanning and phage display provided foundational insights into protein structure and function, the emergence of high-throughput approaches—such as Multiplexed Assays of Variant Effect (MAVEs)—and predictive tools powered by artificial intelligence have vastly expanded our ability to profile mutational landscapes. However, these methods are often constrained by trade-offs between accuracy, scalability, and biological relevance.This dissertation presents the development and application of the GigaAssay, the world’s first high-throughput functional assay capable of delivering both …

Claudin-1-Mediated Signaling And Therapy Resistance In Colorectal Cancer: From Mechanism To Translation, Mark W. Primeaux

Theses & Dissertations

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with metastatic cases showing poor response to chemotherapy due to both intrinsic and acquired therapy resistance. Claudin-1 (CLDN1), a tight junction protein, is overexpressed and mislocalized outside of tight junctions in CRC, where it contributes to an aggressive, metastatic phenotype. Although this causal relationship has been well established, the mechanisms by which CLDN1 promotes tumor progression were unclear due to its lack of intrinsic enzymatic activity. This dissertation investigates the molecular mechanisms through which CLDN1 drives oncogenic signaling, its role in therapy resistance, and its translational potential as both a …

Computational Investigation Of The Structural And Electronic Effects Of Phenyl, Alkyl, And Halogen Fully Substituted Acenes, Emily A A Jarvis, Viraj Jain, Georgia Grace Tully, Peter W. Jarvis

Chemistry and Biochemistry Faculty Works

Acenes are a class of polycyclic aromatic hydrocarbons that may hold promise as organic semiconductors (OSCs) in solar cells and electronic devices. Their instability and poor solubility present challenges that may be improved by replacing the hydrogens with phenyl, halogen or alkyl substituents to sterically induce a helical twist to these otherwise planar molecules. This twisted structure also impacts the optical properties of these molecules. We employ time-dependent density functional theory (TD DFT) to investigate acenes spanning from naphthalene to heptacene. We focus on the structural and electronic effects of fully substituting these molecular backbones to create seven distinct substituent …

Growth Of Cylindrical Micelles And Their Use To Prepare Porous Materials With Tailored Dimensions And Alignment, Mengxue Zhang, Xiaomeng Li, Chuanbing Tang, Morgan Stefik

Faculty Publications

Materials with cylindrical pores are optimal for electrochemical devices and filtration due to their straight paths with minimal tortuosity when aligned. Polymer templates have led to many individual cylindrical architectures however the independent tailoring of pore and wall dimensions has remained elusive. Here short cylindrical micelle templates (PEO-b-PS) with glassy cores enabled the fabrication of sample series with constant cylindrical pore diameter (∼63 nm) and tailored wall thickness (TiO₂, ∼45–100 nm). This ShortCyl series (aspect ratio 4.25) had modest alignment that was attributed to the low free-energy cost for misalignment. Though the plasticized micelles (DCM present) …

Long Intergenic Non-Coding Rna 00511 (Linc00511) Genetic Variations And Haplotype Implication For Colorectal Cancer Susceptibility And Prognosis, Eman Fouad Sanad, Ahmad Abd El Hady, Mohamed Ali, Shorouk Eldash, Nermeen H. Elmorshedy, Farah Ayman, Hams M. Khattab, Amr Maher, Hadeel Ashree, Mahitab Abdelhady, Mazen Mohamed, Ahmed Adel, Sajed Khalil, Omar Alyan, Ahmed Samir, Alhassan A. Bakr, Nadia Hamdy

Pharmacy

Long intergenic non-coding RNA 00,511 (LINC00511) is considered an oncogene for various cancers. However, the association between LINC00511 single nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) remains unclear. Our study aims to study whether LINC00511 SNPs could predict CRC susceptibility or prognosis, an important step-toward precision-health, based on an Egyptian CRC patient cohort. A total of 200 CRC patients and 200 cancer-free controls were genotyped for three LINC00511 SNPs − rs9906859, rs1558535, and rs17780195 using qRT-PCR. Studied SNPs were in strong linkage disequilibrium and moderately correlated in all groups. Genotype association concerning tumor stage, revealed rs1558535 AT and rs17780195 AG …

Effect Of Histidine Tag On The Enzymatic Activity Of Pseudolysin And Its Interaction With The Streptomyces Metalloprotease Inhibitor (Smpi) Protein, Adewale Adeboye Adewole

Electronic Theses and Dissertations

Pseudolysin (PLN) protein is a major virulent factor in Pseudomonas aeruginosa infection. PLN belongs to the family of zinc-dependent metalloproteases. It is naturally inhibited by a smaller protein called streptomyces metalloprotease inhibitor (SMPI), secreted by Streptomyces nigrescens. Previous and current studies demonstrate that the interaction between PLN and SMPI offers unique mechanistic insights for drug development against infections caused by P. aeruginosa. This study investigated the effect of N-terminal Histidine (His) tag on the enzymatic activity of PLN and its interaction with SMPI. His-tagged PLN and SMPI proteins were expressed in bacteria and purified by affinity chromatography …

Advancing Single-Molecule Nanopore Sensing: From Protein Conformation And Metal Binding To Dna Transport Via Hybrid Nanostructures, Matthew J. Odonohue

Multidisciplinary Studies Theses and Dissertations

This dissertation presents the development and application of solid-state and hybrid nanopore platforms for single-molecule analysis of biomolecular interactions. First, a silicon nitride nanopore was employed to characterize the conformational states of the transferrin receptor (TfR), enabling discrimination between its monomeric and dimeric forms, as well as from its ligand, human serum transferrin (hSTf), despite their similar molecular weights. In a separate study, the same nanopore configuration was used to track the real-time binding of titanium ions to transferrin, demonstrating single-molecule sensitivity to metal-induced conformational changes. A hybrid microtubule–solid-state nanopore (MT–SSN) was then engineered, repurposing microtubules as electrostatically anchored conduits …

Cultivation Of Botryococcus Braunii For The Production Of Hydrocarbons Suitable For Fuel Use, Bryan C. Carroll

All Theses

Energy security, rural poverty, and climate change are pressing issues of our time. Biofuels provide a solution to these issues, with a focus on sustainable aviation fuel, SAF, due to compatibility with aircraft infrastructure and energy density. This research aims to review and produce knowledge about a specific microalga, Botryococcus braunii, for its potential for SAF. First a literature review on the process was conducted followed by an experimental study on the impact of aqueous media and inorganic carbon its growth and hydrocarbon content. The literature review found the process consists of cultivation followed by lipid extraction or hydrothermal …

Yizhi Sun: Profile Of The Newest Chbc Faculty Member., Danna Jaimes-Fajardo, Jeremy J. Smith, Lutishoor Salisbury

University Libraries Faculty Publications and Presentations

Presents the research profile of Yizhi Sun, Assistant Professor, Chemistry and Biochemistry department. It highlights his research interests, education, and impact of his research.

Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha

Theses & Dissertations

Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …

Assessing The Impact Of Pll And Ple Concentrations And Aging On Protein Condensates Formation Via Llps, Nabil Harche

Theses, Dissertations and Culminating Projects

Protein droplets, also referred to as condensates, are membrane-less organelles formed through a biophysical process known as liquid-liquid phase separation (LLPS). These structures play an indispensable role in a wide range of cellular functions, including compartmentalizing biochemical reactions, regulating gene expression, and responding to cellular stress. Unlike traditional membrane-bound organelles, these condensates form dynamically and reversibly within the cytoplasm or nucleus, without the need for lipid membranes. The formation of these protein droplets is affected by several physicochemical factors, including pH, temperature, ionic strength, concentration of biomolecules, and specific molecular interactions such as electrostatics and hydrophobic forces. LLPS results in …

Comparative Expression Of Cgmp-Dependent Protein Kinase G (Pkg) From Plasmodium And Toxoplasma, Tsopmo Asaah

Theses, Dissertations and Culminating Projects

Malaria and Toxoplasmosis are life threatening diseases to humans. The search for a cure and control of these diseases is still one of the major challenges of scientists worldwide. In this research we focused on two Malaria species; Plasmodium bergei² (Pb) and Plasmodium falciparum¹ (Pf) and also on Toxoplasma gondii. Part of the life cycle of these organisms is regulated by the enzyme cyclic GMP-dependent protein kinase G (PKG)⁴. This is our drug target in this research. We believe that inhibiting this enzyme will be a great step in fighting these diseases. In this research, we devised a comparative study …

Elucidating The Mechanisms Underlying A Functional Plant-Arbuscular Mycorrhizal Symbiosis Using Omics Approaches, Jasmine Gill

All Dissertations

Arbuscular mycorrhizal fungi (AMF) are obligate biotrophs forming symbiotic association with plants. The plant-AMF symbiosis has gained much attention due to its ability to improve plant nutrient uptake, especially phosphorus, which is often inadequately available to plants due to its limited mobility and complex formation in many soils. Phosphorus (P) is a crucial nutrient for plants, and most phosphate fertilizers are derived from phosphate rock, a finite natural resource. Thus, optimizing P uptake is vital for sustaining crop yields and addressing the needs of a growing global population. Plant-AMF symbioses are significant in this context, as AMF can acquire P …

Small Angle X-Ray Scattering Studies Of Collagenase H Mutant, Colh-E416q, Madelyn Millsap

Graduate Theses and Dissertations

Collagenase H (ColH) from Hathewaya histolytica plays a central role in collagen degradation through endopeptidase and carboxytripeptidase reactions. To better understand how its domain architecture supports these functions, we examined the solution structure of a catalytically inactive mutant, ColH-E416Q, using small-angle X-ray scattering (SAXS). The E416Q mutant is catalytically inactive because the glutamate residue at position 416, which normally functions as a general acid/base during catalysis, is replaced by glutamine—an amide that cannot donate or accept protons effectively, thus disabling the proton transfer steps essential for peptide bond hydrolysis. SAXS results indicate that the E416Q substitution leaves overall domain architecture …

Analysis Of An Ethanol Sensitive Bmp-Nkx2.3-Fgf Signaling Pathway In Pouch Morphogenesis., Hieu Dai Le Vo

Electronic Theses and Dissertations

Craniofacial malformations lie at the heart of Fetal Alcohol Spectrum Disorders (FASD). While there is growing evidence for a genetic component to FASD, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. Bone Morphogenetic Protein (Bmp) signaling pathway dependent pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like nkx2.3 and Fibroblast Growth Factor (Fgf) signaling, may mediate the impact of ethanol on Bmp mutants. Here, I …