Biophysics Commons^™

Microtubule Self-Organization With Active And Passive Crosslinkers, Prashali Chauhan

Dissertations - ALL

Humans have always been trying to unravel principles that guide how things around us function, all the way from galactic ovements to basic building blocks of matter. The physical and chemical properties of ‘biological’ systems govern processes all the way from molecular interactions of proteins to the form and function of individual living organisms. In this work, I focus on the proteins which help give shape and structure to the smallest building block of life, the cell and associated mechanisms of building fundamental cellular architectures, like the mitotic spindle. Mitosis takes place by microtubules aligning themselves in anti-parallel fashion with …

Evaluating Bmx-001 As A Selective Radioprotector For Healthy Tissue In Pelvic Cancers, Molly Myers

Theses & Dissertations

Pelvic cancers, including rectal, anal, and prostate cancer, are relatively survivable cancers with high five-year survival rates, partially due to the addition of radiation to treatment regimens. Radiation confers excellent tumor control, but also causes damage to surrounding tissue, resulting in both short-term and long-term side effects. In a patient population that is surviving longer after treatment, limiting the impact of side effects is instrumental to improving patient quality of life. Radiation-induced ROS is instrumental in causing these side effects and provides a unique opportunity to protect healthy tissue from damage while sensitizing cancer tissue to treatment, as cancer cells …

Structural Basis Of A Class Ii Ribonucleotide Reductase Found If Mycobacterium Tuberculosis, Leah Jacob

Student Scholar Symposium

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health challenge, particularly due to its ability to enter a dormant, drug-tolerant state that enables long-term persistence within the host. Just before dormancy, Mtb replicates its entire genome creating DNA precursors for when the infection reactivates. Ribonucleotide reductases (RNRs) play a critical role in bacterial survival by catalyzing the conversion of ribonucleotides into deoxyribonucleotides, a necessary step for DNA replication and repair. The class II RNR, NrdZ, has been implicated in facilitating Mtb persistence under hypoxic stress conditions, yet its structural and mechanistic function remains largely uncharacterized. …

Unsaturated Fatty Acid Oil-Based Microdroplets: A Promising Novel Class Of Microdroplets, Ramiz S. Alejilat

Seton Hall University Dissertations and Theses (ETDs)

Droplet-based microfluidics has rapidly advanced numerous fields, including chemistry, biology, materials science, medicine, food science, and cosmetics. In these systems, fluorocarbon oil combined with fluorinated surfactants is the preferred medium for fluid encapsulation, offering exceptional stability and biocompatibility essential for sensitive biological and chemical processes. However, growing concerns about the environmental and biological risks associated with fluorinated chemicals have prompted a search for alternatives.

This study is the first to explore the use of unsaturated fatty acids derived from emu oil for microdroplet formation. We characterized droplet formation based on flow rates and the presence non-fluorinated surfactant at a certain …

[Kadel] A Multilevel Extension Of Boolean Networks Captures Topologically-Stable Hybrid Attractors, Kishore Hari

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

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 …

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, …

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 …

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 …

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 …

Elucidating The Roles Of Eukaryotic Initiation Factors Involved In Dap5 Mediated Translation, Jacob Nk Quartey

Dissertations, Theses, and Capstone Projects

Translation initiation in eukaryotes is a highly regulated process essential for accurate protein synthesis. It is a dynamic process that involves a complex interplay between messenger RNAs (mRNAs), ribosomal subunits, and a host of initiation factors, ensuring precise start codon selection and the subsequent assembly of the translation machinery. This process has well been known to be mediated by the eukaryotic Initiation Factor (eIF4F), which consists of the cap binding protein eIF4E, the scaffolding protein eIF4GI, and the helicase factor eIF4A.The recognition and binding of eIF4E to the m⁷G cap structure of the mRNA is essential for the …

Biophysical Analysis Of S100a12 And The Nucleosome Core Particle, Christopher Diforte Jr.

Dissertations, Theses, and Capstone Projects

Calcium signaling and chromatin remodeling are fundamental regulatory processes that control protein activity and gene expression, respectively. This thesis investigates the molecular mechanisms by which local ligand binding and structural perturbations propagate allosteric effects across larger protein systems, using two distinct yet mechanistically analogous models: the calcium binding protein S100A12 and the nucleosome core particle. These studies are unified by a shared emphasis on how physical forces govern biological function.

In the first part, we explore calcium mediated allostery in S100A12, focusing on the distinct roles of its two EF-hand calcium binding loops (EF-I and EF-II). Through a combination of …

Characterization Of Sars-Cov-2 Replication And Transcription Complexes Via Structural And Evolutionary Approaches, Amelie Ghirardo, Ben Shabatian, Avishai Aghelian, Kyle Tau, Eleonora Gianti

Undergraduate Research

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused around 700M cases and over 7M COVID-19-related deaths recorded worldwide (World Health Organization, March 2025). Aiming to effectively combat this and other disease-causing Coronaviruses (CoV), unprecedented research efforts led to the development of new vaccines and antiviral therapies. Due to emergence of variants of concern (VOCs) with increased transmissibility, immune evasion from vaccination, and potential to resist the available treatments, SARS-CoV-2 continues to represent a major threat to global health. Hence, there is a pressing need to discover new antivirals with broad-spectrum efficacy against multiple SARS-CoV-2 variants and related CoVs. This project …

Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew

Theses & Dissertations

Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …

Implications Of Type Iv Pilus Retraction For Dna Uptake By Acinetobacter Baumannii, Yafan Yu

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Horizontal gene transfer (HGT) via natural competence allows bacteria to incorporate extracellular DNA (eDNA) into their genomes, facilitating genetic diversity and adaptation. In Acinetobacter species, natural competence depends on DNA binding and uptake mediated by type IV pili (T4P). T4P are dynamic extracellular filaments composed primarily of the major pilin subunit PilA, along with a few minor subunits. T4P drive a range of cellular functions including twitching motility, biofilm formation, and DNA uptake, with some functions dependent on pilus retraction and others not. However, how Acinetobacter T4P bind DNA and how T4P/eDNA interactions impact biofilm formation remain unclear. Here, I …

Amyloid Aggregation And Mitigation, Zhenzhen Zhang

All Dissertations

The buildup of protein in tissues and organs plays a major role in unfunctional several serious diseases, including Alzheimer’s disease, Parkinson’s disease, and Type 2 diabetes, each tied to specific proteins that form harmful amyloid deposits. Amyloid aggregation typically follows a sigmoidal kinetic curve, beginning with a slow lag phase, followed by rapid fibril growth, and eventually reaching a plateau where mature, stable fibrils are formed. However, the early stage of aggregation remains particularly difficult to capture experimentally due to the highly dynamic nature and low abundance of small oligomeric species. In this dissertation, we employed discrete molecular dynamics (DMD) …

Developing An Unfolding-Incorporated Coarse-Grained Polymer Model For Fibrinogen To Study The Mechanical Behaviour, Vivek Sharma, Poulomi Sadhukhan

Northeast Journal of Complex Systems (NEJCS)

Fibrinogen is a protein found in blood that forms Fibrin polymer network to build a clot during wound healing process when there is a cut in the blood vessel. The fibrin fiber is highly stretchable and shows a complex mechanical properties. The fibrin monomer, Fibrinogen, has a very complex structure which is responsible for its unusual elastic behaviour. In this work, we focus on mechanism of unfolding of D-domain of Fibrinogen, and study its effect in the mechanical behaviour. We develop a coarse-grained (CG) bead-spring model for Fibrinogen which captures the unfolding of folded D-domains along with other necessary structural …

The Fractography Of Bone: Impact Of Flat Bone And The Story It Tells, Abigail Hoffmeister, Chase Freeman, Brandon Mendoza, Nathaniel Fitch, Annie Markarian, Jack Tran, Joshua Lau, Nicholas Tran

Seaver College Research And Scholarly Achievement Symposium

Fractography as a method for fracture analysis has been applied widely to materials that range from glass to ceramics and polymers of varying compositions. Very limited research has been done, however, to apply this knowledge of fractography and fracture patterns to bone. With the goal of telling the story of how a bone was broken, this research focuses on observing known patterns of fracture in polymers, and applying these patterns to bone. For the purposes of this research, porcine scapulae were acquired, dissected from surrounding tissue, and broken using a standardized weight drop at varying heights. The fractured bone was …

Host P53 Expression During C. Parvum Infection…Does The Virus Play A Role?, Jasdeep Kaur Dhanoa

Biochemistry and Molecular Biology

C. parvum infection induces significant host cellular stress responses, particularly through the modulation of p53 expression underscoring its potential involvement in gastrointestinal malignancies. Understanding these mechanisms is crucial for developing targeted therapeutic interventions. This study investigated the effects of C. parvum infection on host p53 dynamics in HCT-8 cells and assessed the impact of antiviral agents Lamivudine and Amantadine on the virus CSpV1 present within the parasite C. parvum. Further, the study focuses on whether the p53 effect changes with the presence or absence of CSpV1. The p53 assay results showed a constant increase in p53 activity after infection of …

Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

No abstract provided.

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

Probing The Stability Of Designed Protein, Axel Irianni, Shuvo Chakraborty, Maral Afshinpour

SDSU Data Science Symposium

Naturally occurring proteins have evolved to perform specific biochemical functions, and their amino acid sequences are optimized for those functions rather than for stability. Enhancing protein stability without compromising its function is highly desirable for biotechnological applications, such as vaccine design. Computational protein design algorithms offer a solution by making targeted amino acid changes to the native protein sequence, potentially enhancing stability without the need for the lengthy, labor-intensive, and costly experimental processes typically involved in stabilizing proteins. There are various categories of computational protein design algorithms, and it remains unclear which approach is the most effective. In this study, …

Conformation And Membrane Topology Of The N-Terminal Ectodomain Of Influenza A M2 Protein, Kyra C. Roepke , '24, Kathleen P. Howard

Chemistry & Biochemistry Faculty Works

The N-terminal ectodomain of the influenza A M2 protein is a target for universal influenza vaccine development and novel antiviral strategies. Despite the significance of this domain, it is poorly understood and most structural studies of the M2 protein have disregarded the N-terminal ectodomain in their analyses. Here, we report conformational properties and describe insights into the membrane topology of sites along the N-terminal ectodomain. Full-length M2 protein is embedded in lipid bilayer nanodiscs and studied using site-directed spin labeling electron paramagnetic resonance spectroscopy. Results are consistent with a turn in the middle of the ectodomain that changes in proximity …

Ivy Proteins As Guardians Of Bacterial Cell Wall Integrity: Regulation Of Lytic Transglycosylases Explored, Aamna Aijaz, Trinity E. Alamutu, Vy T. Dao, Nathaniel R. Davis, Michael D. Landers, Nykolas K. Mackevicius, Liliana Ortiz, Irina F. Padilla-Montoya, Kacy J. Smith, Maria L. Snyder, Anthony J. Stefanie, Blaise M. Williams, Thomas C. Leeper

The Kennesaw Journal of Undergraduate Research

Lytic transglycosylases (LTs) are bacterial enzymes involved in biosynthesis and maintenance of the peptidoglycan cell wall. LTs are reported to be regulated by two paralogs of Inhibitor of Vertebrate Lysozymes: Ivyp1 and Ivyp2. This study investigated the regulatory dynamics between the soluble LT (SltB1), and Ivy paralogs as putative regulators in Pseudomonas aeruginosa (PA). The secondary objective was to delineate the critical roles played by a glutamic acid at position 135 in SltB1 and a histidine at position 62 in Ivyp1 in governing their molecular interaction through site directed mutagenesis. Isolated SltB1 shows no lytic activity in our assay, in …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García

Dissertations, Theses, and Capstone Projects

The study of biological systems is, inherently, the study of very complex systems. This is essentially due to the fact that they are made up of numerous, often very complicated, interactions between an extensive number of components. Often necessitating an abundance of quantitative parameters and details for a precise description. The human brain for ex- ample, consisting of ∼ 80 billion neurons with ∼ 800 to 100 trillion connections between them, each of them depending on a large set of parameters. Even simpler examples such as bacterial organisms, such as E. coli and B. subtilis, which we focus on …

Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul

All ETDs from UAB

RNA-binding proteins (RBPs) play critical roles in RNA processing and regulation. Among these RBPs, U1-70K is a key protein involved in RNA processing, nuclear speckle formation, and has implications in neurodegenerative diseases such as Alzheimer's. Despite its significance in transcription, RNA processing, nuclear speckle formation, and nonsense-mediated decay, studies on U1-70K have been limited primarily to its well-structured N-terminal domain due to challenges in solubilizing and expressing the full-length protein. In this dissertation, we address these challenges by optimizing cell strain and co expressing DnaK and DnaJ, enabling the successful expression, solubilization, and purification of full-length U1-70K. Using fluorescence polarization …

Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason

All ETDs from UAB

The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions …

Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases, Jaskamaljot Kaur Banwait

All ETDs from UAB

Escherichia coli ClpB and Saccharomyces cerevisiae Hsp104 are part of the Hsp100 family of proteins responsible for maintaining protein homeostasis in a cell during heat-stress conditions. Structurally, ClpB and Hsp104, in their active state, assemble into hexameric ring complexes with a hollow axial channel. Functionally, these enzymes are hypothesized to couple energy from ATP binding and hydrolysis to unfold protein substrates and translocate them through their axial channel. However, the molecular mechanisms of protein unfolding and translocation catalyzed by both ClpB and Hsp104 are not well understood. In this dissertation, we report the development of a single-turnover transient state kinetics …

Protein-Metal Interactions Of A-Synuclein And Bioactive Transition Metals Via Molecular Dynamics, Gonzalo R. Vazquez

Theses and Dissertations

Parkinson’s Disease (PD) is a neurodegenerative movement disorder which has been found to target the dopaminergic neurons of the substantia nigra. It is characterized by the formation of masses known as Lewy Bodies, formed by aggregates of the intrinsically disordered protein (IDP) -synuclein (asyn). Research suggests that alpha synuclein can undergo aggregation in the presence of heavy metals, which may accumulate in the body through a variety of mechanisms. To study how metals may play a role in wildtype (WT) asyn aggregation, MD simulation of the protein was performed in the presence of bioactive transition metals including Fe2+, Fe3+, Cu+, …