Life Sciences Commons^™

From Venom To Medicine: Harnessing Animal Toxins For Drug Discovery, Christine Vega, Ying Jia

Research Colloquium

Background: Drug development research has long focused on synthesizing novel therapeutics while overlooking isolation from naturally available sources such as animal venoms. Recently, the discovery of the therapeutic effects of highly bioavailable animal venom caused the field of venom research to soar in popularity. Animal venom serves as a natural, sophisticated tool optimized over millions of years by evolution with the ability to bind to ion channels such as nAChRs, non-specific ligand-gated ion channels distributed throughout the human nervous system. However, purifying individual venom toxins from crude venom is challenging due to its availability. Therefore, synthesizing large quantities of venom …

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 …

Resolution Of Physics And Deep Learning-Based Protein Engineering Filters: A Case Study With A Lipase For Industrial Substrate Hydrolysis, Spencer Gardiner, Peter Dollinger, Filip Kovacic, Jörge Pietruszka, Daniel Ess, Karl-Erich Jaeger, Gunnar F. Schröder, Dennis Della Corte

Faculty Publications

Computational enzyme design remains a powerful yet imperfect tool for optimizing biocatalysts, especially when targeting non-natural substrates. Using design tools we investigated Pseudomonas aeruginosa LipA, a lipase with a flexible lid domain crucial for substrate binding and turnover, aiming to enhance its hydrolysis of the industrially relevant substrate Roche ester. We generated an initial set of single-point mutations based on structural proximity to the active site and evaluated their effects using a computational pipeline integrating molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and ensemble-based energy scoring. While we identified several active variants, attempts to rank them by activity …

Binding Of A [2fe-2s] Cluster Drives Dimerization Of Ferric Uptake Regulator (Fur) In Escherichia Coli, Fatemeh Najafi, Aidan G. Purcell, Finbar H. Homes, Huangen Ding

Faculty Publications

The ferric uptake regulator (Fur) is a global transcription factor that reversibly binds an iron-sulfur [2Fe-2S] cluster via the cysteine residues (site 3) in response to elevation of intracellular free Fe content in Escherichia coli. Here, we report that when E. coli Fur is expressed in E. coli cells grown in M9 medium supplemented with Fe or zinc (Zn), purified Fur binds a [2Fe-2S] cluster or Zn(II), respectively. While apo-form Fur is a monomer and has no DNA-binding activity, both the [2Fe-2S] cluster-bound Fur and the Zn(II)-bound Fur are homodimers and have a similar binding activity for the DNA sequence …

Analysis Of Telomeric Conformational Dynamics At The Single Molecule Level, Arianna Lacen

All ETDs from UAB

In eukaryotes, the telomere serves as a safeguard against DNA damage and loss during replication and other events. To do so, telomeric DNA folds into a variety of protective secondary and tertiary structures whose formation and conformational dynamics have not been well characterized. We have identified a slow conformational rearrangement in telomeric single stranded DNA that results in a G-Quadruplex (G4) that cannot be unfolded by a complementary strand. We have also determined how the accessibility of G4 forming sequences changes in response to different high K+ environments, which may have implications on how the nascent telomeric overhang interacts with …

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 …

The Effects Of Tfeα And Promoter Sequence On Early Events In Archaeal Transcription Initiation, Madolyn Toli

Dissertations and Theses

Expression of genes is dependent on promoter sequences in DNA, which direct transcription by RNA polymerase. Transcription factors interact with promoters and RNAP and are often conserved and are essential for proper gene expression. In this thesis, a functional region of archaeal TFEα, homologous to eukaryotic TFIIEα, has been identified, and specific amino acids in these regions have been determined to have significant importance in TFEα's ability to promote transcription in early initiation. All three Domains of life encode a 16S rRNA promoter, which is responsible for production of the 16S portion of ribosome. Transcription with this promoter is not …

Stayin' Alive (Even Without Oxygen): Retinal Development In Austrofundulus Limnaeus, Carmen Zecilia Rodriguez

Dissertations and Theses

The vertebrate eye is one of the most metabolically active organs in the body and is particularly sensitive to environmental stressors such as oxygen deprivation. Understanding how eye development proceeds under such conditions can provide critical insights into mechanisms of cellular resilience, tissue organization, and developmental plasticity. The annual killifish Austrofundulus limnaeus represents a unique model for investigating these processes due to its remarkable tolerance to anoxia during embryogenesis. However, the wild-type form is heavily pigmented, limiting the effectiveness of traditional imaging techniques for studying eye development. This thesis characterizes eye development and anoxia resilience in both wild-type and melanin-deficient …

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.

Gene Expression Of Anthocyanin Pigments In The California Native Plant Leptosiphon Parviflorus: Interactions Between Flower Color Morphology And Abiotic Stressors, Weston Gonor

Master's Theses

For plants to survive in harsh conditions imposed by abiotic stressors, they must develop mechanisms of adaptation. One of the common types of adaptation seen in plants is the production of anthocyanin pigments, which have been shown to protect plants from UV radiation, metabolic stress, and drought. In this study, we used the flower color polymorphic species Leptosiphon parviflorus to investigate the role of anthocyanin pigments in protecting plants from abiotic stress. To accomplish this, RNA samples were taken from flower, leaf and root tissue of different flower color morphs of Leptosiphon parviflorus (Polemoniaceae) grown in high magnesium and water …

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 …

An Integrated Skeletal Muscle Methylome-Transcriptome Profile In Pre-Clinical Colorectal Cancer Cachexia Models And Chemotherapy Aggravating The Effects Of Cachexia, Ana Regina Cabrera Ayuso

Graduate Theses and Dissertations

Cancer cachexia is a wasting syndrome characterized by the loss of skeletal muscle affecting cancer patients’ independence and quality of life. Cancer cachexia affects up to 80% of cancer patients and is responsible for 30-40% of cancer-related deaths. Previous studies have demonstrated sex-specific differences in the onset and progression of cancer cachexia; however, these differences remain underexplored. To date, pharmacological and nutritional interventions are largely ineffective in preventing or reversing cachexia. Chemotherapy, a first-line cancer treatment, is known to trigger cachexia by itself complicating prognosis and therapy response. In addition, epigenetic alterations, such as DNA methylation (DNAm), are known to …

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 …

Investigating The Role Of Early Growth Response 1 (Egr1) Gene In Riluzole-Induced Apoptosis In Osteosarcoma, Syeda Maryam Azeem

Dissertations, Theses, and Capstone Projects

Osteosarcoma is a rare but aggressive bone malignancy most commonly affecting adolescents and young adults (AYA). With 5-year survival rate stagnating over the last four decades despite the advancements in multi-modal therapy, drug repurposing offers a rapid path to new osteosarcoma treatments. Recent studies suggest that Riluzole, a drug approved for amyotrophic lateral sclerosis (ALS), may be repurposed for osteosarcoma treatment due to its ability to slow tumor progression and induce apoptosis. Previously, we have shown that Riluzole increases reactive oxygen species (ROS), activating c-Abl, which phosphorylates YAP in the nucleus. YAP then forms a complex with p73 to enhance …

Structural Characterization Of A Tarantula Toxin And Its Interactions With Lipid Bilayers And Voltage-Gated Sodium Channels, Krishnakoli Adhikary

Dissertations, Theses, and Capstone Projects

Voltage-gated ion channels are membrane protein complexes. They allow the selective flow of their respective ions down an electrochemical gradient through a central ion conduction pore surrounded by four voltage-sensing domains (VSDs). Various neurological and cardiovascular diseases are caused by mutations in voltage-gated ion channels (VGICs). One of the biggest challenges today is addiction to opioid medication. Coming up with non-opioid drug leads can be a real blessing for society. This is where voltage-gated sodium channel research comes in. Na_v1.7, Na_v1.8, and Na_v1.9 are responsible for pain sensations. Loss or gain of function in …

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, …

The Sonic Hedgehog Effector Smoothened Modulates Cholinergic Interneuron Activity, Physiology, And Striatum-Dependent Behaviors, Santiago Uribe-Cano

Dissertations, Theses, and Capstone Projects

The striatum is a central node in action selection and associative learning, integrating cortical, thalamic, and neuromodulatory input. Among its principal modulators, dopamine (DA) and acetylcholine (ACh) are known for their temporally coordinated yet mechanistically distinct influences on striatal output. However, the upstream signals that regulate their dynamic interplay, particularly within cholinergic interneurons (CINs)—the primary source of striatal ACh—remain incompletely characterized. This dissertation investigates the role of Smoothened (Smo), a G protein-coupled receptor (GPCR) effector of Sonic Hedgehog (Shh) signaling, in modulating ACh signaling dynamics in the striatum.

Building on evidence that midbrain DA neurons co-release Shh and that CINs …

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 …

Design And Development Of A Standalone Digital Holographic Microscope Employing Phase-Driven Reconstruction And Classification For Biomedical Imaging And Optical Diagnostics, Charlotte Kyeremah

Graduate Doctoral Dissertations

Access to advanced biomedical imaging technologies remains a significant challenge in resource-limited settings, especially for early disease detection and monitoring of diseases such as malaria, HIV, and other blood-borne diseases. Although point-of-care (POC) devices have gained popularity in global health, many rely on antibody-based tests, lateral flow strips, or optical readouts that often lack quantitative capabilities, sensitivity to early infections, or versatility in different diagnostic targets. In addition, these systems are typically dependent on disposable reagents or manual interpretation, which limits their effectiveness in remote areas. Digital Holographic Microscopy (DHM) presents a promising alternative as a label-free imaging method capable …

Centrosomal And Non-Centrosomal Microtubule Networks Coordinate To Drive Nuclear Dynamics In Developing Epithelium, Rashmi Budhathoki

Electronic Theses and Dissertations

The morphogenesis of developing tissues relies on extensive cellular rearrangements in shape, position, and identity. A key process in reshaping tissues is cell intercalation-driven elongation, where epithelial cells align and intercalate along a common axis. Typically, analyses focus on how peripheral cortical forces influence cell shape changes. Less attention is given to how inhomogeneities in internal structures, particularly the nucleus, impact cell shaping. Here, we examine how pulsed contractile and extension dynamics interact with the nucleus in elongating Drosophila embryos. Our data show that tightly packed nuclei in apical layers hinder tissue remodeling/oscillatory behaviors. We identify two mechanisms for resolving …

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 …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

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 …

Effect Of Osmolytes On The Interplay Of Water Protein And Dna In Ecori Dna Recognition Using Molecular Dynamics Simulations, Aathithya D

Theses and Dissertations

EcoRI is a type II restriction endonuclease that has been widely used as a model system to study protein-DNA interaction owing to its high degree of specificity. This enzyme does not recognize even a single basepair change in its recognition sequence, (GAATTC)2, under normal conditions. However, in the presence of osmolytes, such as glycerol and DMSO, the specificity of EcoRI is slightly relaxed and recognizes sequences that differ from its cognate sequence in the first basepair position. This relaxed specificity has been attributed to the dehydration of the EcoRI-DNA which presumably results in tighter complex formation and subsequent catalysis. However, …