Other Biochemistry, Biophysics, and Structural Biology Commons^™

Mapping Nucleosome Stability: Linking Oncogenic Structural Alterations To Long-Range Allosteric Communication, Augustine C. Onyema

Dissertations, Theses, and Capstone Projects

The nucleosome core particle (NCP) is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. How DNA communicates with histones, and how this information propagates through the histone, has been suggested to be a cooperative process. Here, I investigate the molecular consequences of two mutations, H2BE76K and H4R92T, using 36 µs of all-atom molecular dynamics simulations on Anton2. I also characterize the kinetic correlation within histone/DNA domains via conditional activity (CONDACT) using the dihedral angle as our degrees of …

Somatic Prosthetics For Planetary Resonance, Disha Dharesh Kumar R

Masters Theses

This thesis investigates how industrial design can transcend extractive technological paradigms in favor of relational interfaces that foster planetary attunement. Framing the climate crisis as a 'crisis of imagination', the research challenges the Western bifurcation of nature and culture by drawing on Indic cosmologies- which recognize stones, plants, and ecosystems as conscious at different levels and participants in a shared cosmic field. By synthesizing research in Biosemiotics, Quantum Information Pansycishm, and Neuroscience, the project redefines intelligence as a distributed, more-than-human phenomenon.

The research materializes as a speculative design artifact: a device that functions as a somatic prosthetic for planetary resonance. …

Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani

Honors Theses

Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …

Computational And Functional Characterization Of Terebrid Venom Peptides, Favour T. Achimba

Dissertations, Theses, and Capstone Projects

Venom peptides represent a natural repertoire of bioactive compounds that are potent modulators of ion channels. Teretoxins, venom peptides from terebrid snails, remain underexplored despite their structural and functional diversity. This thesis is the first to comprehensively explore the structure and function of teretoxins using a comparative computational sequence and structure model followed by experimental assays. The majority of the functional focus has been on identifying the ion channel molecular targets of uncharacterized teretoxins. Teretoxins, like other venom peptides, are hypothesized to manipulate the cellular function of a diversity of ion channels. Dysregulation of ion channels leads to several …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Interaction Of The Gram-Positive Human Pathogen Staphylococcus Aureus With Host Lipids, Sharanya Paul

Theses and Dissertations

Staphylococcus aureus is a prominent pathogen that is known to incorporate straight-chain unsaturated fatty acids (SCUFAs) into its lipids in addition to the normally biosynthesized branched-chain fatty acids (BCFAs) and straight-chain fatty acids (SCFAs). Furthermore, it has recently been shown that the incorporation of oleic acid into S. aureus lipids significantly enhanced the growth of the organism at low temperatures due to the greater fluidity imparted to the membrane. Together with others in the Wilkinson and Dahl laboratory, I have shown that low-temperature growth is enhanced by various SCUFAs, including the human antimicrobial fatty acids sapienic acid, linoleic acid, and …

Comparing The Differences Of Hsp90Α And Hsp90Β In Native Protein Complex Incorporation, Daryna Serediuk

Honors Theses and Capstones

Epichaperomes are long-lasting, stable assemblies of chaperones, co-chaperones, and associated factors that facilitate cell survival in maladaptive cellular states. Their inhibition has emerged as an attractive therapeutic strategy for the treatment of cancer and neurodegenerative diseases (Rodina et al., 2016). Epichaperomes are hallmarks of robust proliferation in cancer cell populations across many cancer types and are abundantly present in several stem cell varieties, including induced pluripotent stem cells, human embryonic kidney cells, and cancer stem cells (Kishinevsky et al., 2018).

The core protein of the eukaryotic heat shock protein machinery, Heat Shock Protein 90 (Hsp90), is a central chaperone that …

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, …

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 …

A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza

MUSC Theses and Dissertations

Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …

Foldit Education Mode, Brett Schulz

Electronic Theses and Dissertations

Foldit education mode is a puzzle campaign within the protein folding video game Foldit. Education mode, initially designed as a classroom supplement for undergraduate biochemistry courses, has been expanded to provide a more comprehensive learning tool to players without a background in biochemistry. The edited and added levels teach players about protein biochemistry through playing puzzles designed to convey information and gameplay mechanics. The new Foldit education mode campaign features 49 levels grouped into 11 categories. The campaign has 6 new levels designed specifically for education mode and 4 levels adapted from the traditional Foldit campaign for use within education …

Structural And Functional Lessons Learned About Regulation Of Enterotoxigenic E. Coli Virulence Regulatory Factor, Rns, Jessica Dianne Tolbert

Dartmouth College Ph.D Dissertations

Antibiotic resistance has exacerbated the global health crisis of diarrheal diseases caused by enteric bacterial pathogens. Investigating pathogens, such as Enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae (cholera), helps to uncover mechanisms for the inhibition of virulence gene expression. A notable member of the AraC transcription factor family in ETEC, Rns, regulates virulence factors including pili and fimbriae, which are essential for adherence and colonization of the intestinal epithelial layer. This microbe–host interaction initiates the release of toxins, leading to the water and ion loss in clinically diagnosed as diarrhea.

In the canonical N-terminal domain of Rns, mutagenesis of the …

A Qualitative Nmr And Histological Analysis Of Adipocere Formation In Different Aqueous Environments Using Sus Scrofa Models, Mia M. Sorrentino

Student Theses

Adipocere is a wax-like crust that has the potential to form over corpses in moist, humid, and anaerobic environments, preserving them in a process similar to that of mummification. The substance can be identified within 3-6 months postmortem and is characterized by the ratio of saturated fatty acids to unsaturated fatty acids. Palmitic acid and stearic acid are the most abundant in comparison to myristic and oleic acids. The goal of this study was to investigate factors affecting adipocere formation in different aqueous environments. Pork belly samples were submerged in water samples collected from different places around New York City …

Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie

LSU Doctoral Dissertations

Embryos of Artemia franciscana survive harsh conditions in diapause and anoxia-induced quiescence for years by undergoing deep metabolic transitions. I investigated the relationship between phosphorylation of pyruvate dehydrogenase (PDH) and carbon flux to the tricarboxylic acid (TCA) cycle during metabolic depression. The difference in catalytic activity of the PDH complex (PDC) in maximally phosphorylated and dephosphorylated samples was 16.5-fold. Western blot analysis confirmed the changes in phosphorylation of PDH. Analysis of PDH expression in diapause and post-diapause embryos via phospho-PDH showed no significant differences. Investigation of post-diapause embryos under anoxia showed that phosphorylation of PDH decreased and activated the enzyme. …

Raman Spectroscopy For Rapid Quantification Of Macronutrients In Heirloom Beans, K. Chandler Williams

Graduate Theses, Dissertations, and Problem Reports (ETD)

Quantification of macronutrients in food requires a large investment in facilities and instrumentation as well as ongoing expenses of labor, reagents, and hazardous waste disposal. These costs pose a significant barrier to determining macronutrient quantities in the thousands of uncharacterized landrace and heirloom crops and discourage traditional crop breeding projects from ensuring that their selected crops maintain desirable macronutrient profiles in addition to target agronomic traits. Our objective was to test whether a hand-held Raman spectrometer—a technology which has found use in plant disease diagnostics but remains largely overlooked in nutrient quantification-- could provide a feasible means for quantifying the …

Polymeric Sumo-2/3 Chain Signals Are Antagonistically Regulated By The Sumo-Targeted Ubiquitin E3 Ligase Rnf4 And The Sumo-Specific Isopeptidase Senp6, Shaniah A. Irving M.A., Xiang-Dong Zhang Ph.D.

Biology Theses

Polymeric SUMO-2/3 chain modification is critical for chromosome segregation, DNA damage repair, genome stability, stress responses, and protein degradation. However, how these signals are regulated remains poorly understood. Both the SUMO-targeted ubiquitin E3 ligase (STUbL) RNF4 and the SUMO-specific isopeptidase SENP6 recognize poly-SUMO-2/3 chains through multiple SUMO-interacting motifs (SIMs). RNF4 contains four tandem SIMs within a short (~80 amino acids) region, whereas SENP6 possesses eight SIMs spanning a much larger (~500 amino acids) domain.

Our preliminary results show that overexpressing an RNF4 N-terminal fragment containing four tandem SIMs (wild type, WT), but not an inactive SIMs mutant (Mut), increases levels …

Model-Based Comparison Of Biological Organism And Electro-Mechanical System Resiliency Strategies, Nicholas Ratycz

Mechanical Engineering Undergraduate Honors Theses

Bio-inspired design has been used by many engineers to solve difficult problems or to make manufacturing processes more efficient. Biomimetics is the study of implementing the structure or function of biological substances, materials, mechanisms, and processes onto artificial ones that mimic the original. The goal of the BIASD tool is to provide bio-inspiration for engineers by studying the fault-adaptive strategies that biological systems use, rather than just their structure or function. In this thesis, the fault adaptive strategies of both a biological example and that of a real cubesat are compared using three types of model-based system diagrams to show …

Identification Of A Novel Target For Declustering Supernumerary Centrosomes In Triple Negative Breast Cancer, Priyanga J

Theses and Dissertations

Triple-negative breast cancer (TNBC) confers considerable interventional challenge owing to its massive heterogeneity, aggression and metastatic prowess. These facets are attributed to chromosomal instability (CIN), a feature consequent to TNBC cell’s ability to harbor more than two centrosomes (supernumerary centrosomes; SNCs).

In principle, if a normal cell possesses SNCs, uneven pull forces are generated consequent to multipolar spindle, which activates cellular surveillance. This ensures error-free mitosis by either repairing the error or, in an irreparable condition, driving cells to death. This averts the possibility of aneuploidy (fundamental to tumorigenesis).

Unfortunately, TNBC cells, despite harboring SNCs, have devised a survival strategy …

Single-Molecule Pulldown (Simpull) For Detection Of Gpcr Complexes In Mammalian Cells, Julie M. Kraft

Theses and Dissertations

G protein-coupled receptors (GPCRs) constitute the most numerous and diverse superfamily of cell membrane receptors. While GPCRs can perform signal transduction as monomers, evidence suggests they also function as homo- and hetero- dimers and oligomers. These diverse quaternary structures can affect GPCRs’ downstream cellular signaling, pharmacological properties, and regulation of internalization.

The single-molecule pulldown (SiMPull) assay combines a co-immunoprecipitation assay with single-molecule total internal reflection fluorescence (TIRF) microscopy and can be used to probe the stoichiometry of GPCR oligomers in mammalian cells.

This project replicates the SiMPull assay by confirming the quaternary structure of mGluR2 homodimers. Plasmid constructs SNAP-mGluR2-HA and …

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

Nanodiscs: A Novel Approach To The Study Of The Methionine Abc Transporter System, Michael T. Winslow

Master's Theses

Membrane transporter proteins play the vital role of moving compounds in and out of the cell and are essential for all living organisms. ATP Binding Cassette (ABC) family transporters function both as importers and exporters in prokaryotes. MetNI is an E. coli Type I ABC transporter responsible for the uptake of methionine into the cytosol from the cell periplasmic space through the cell membrane to maintain intracellular methionine pools. ABC transporters, like other membrane proteins, are most often mechanistically and structurally studied in vitro, solubilized by detergents. However, detergent micelles may affect the conformational changes of membrane proteins relative to …

Fbg Αc 389 – 402 Modulates Factor Xiii Crosslinking In The Fibrinogen Αc Region., Francis Dean Orlina Ablan

Electronic Theses and Dissertations

Fibrinogen (Fbg) is a coagulation protein critical for clot formation. Coagulation Factor XIII (FXIII) is a calcium-dependent transglutaminase that crosslinks reactive glutamines (Q) and lysines (K) between fibrin and other anti-fibrinolytic proteins. In the presence of Ca²⁺, FXIII could be activated non-proteolytically (FXIII-A°), or proteolytically by thrombin (FXIII-A*). Significant increases in clot stability and red blood cell retention are linked to FXIII activity in the fibrinogen αC region (Fbg Aα 221 – 610). This region contains several FXIII-reactive glutamines and lysines, as well as a binding site for FXIII-A* (Fbg αC 389 – 402) that includes a key …

Solving The Cable Equation, A Second-Order Time Dependent Pde For Non-Ideal Cables With Action Potentials In The Mammalian Brain Using Kss Methods, Nirmohi Charbe

Master's Theses

In this thesis we shall perform the comparisons of a Krylov Subspace Spectral method with Forward Euler, Backward Euler and Crank-Nicolson to solve the Cable Equation. The Cable Equation measures action potentials in axons in a mammalian brain treated as an ideal cable in the first part of the study. We shall subject this problem to the further assumption of a non-ideal cable. Assume a non-uniform cross section area along the longitudinal axis. At the present time, the effects of torsion, curvature and material capacitance are ignored. There is particular interest to generalize the application of the PDEs including and …

Antimicrobial Activity And Mechanism Of Amyloid Proteins And Synthetic Conjugated Polyelectrolytes, Fahimeh Maghsoodi

Nanoscience and Microsystems ETDs

Although the exact cause of Alzheimer’s disease (AD) is still unknown, it is widely considered that the accumulation of amyloid plaques composed of the amyloid-β (Aβ) peptide in the brain is linked to neurodegeneration. Co-localization of viral DNA with Aβ plaques, the association of brain infection and AD, and research indicating the protective effect of Aβ against bacteria and fungi in mice and human cells have led to the hypothesis that Aβ expression and deposition may be central to its function as an antimicrobial peptide (AMP). In my thesis research, we seek to elucidate how Aβ functions as an AMP …

Effects Of Group Ii Metal Binding On The Stability Of Dna I-Motif Structures, Charlotte Powers

Honors Theses

B-form DNA can adopt alternative structures while in superhelical duress. Alternative DNA structures are favored when there is an asymmetric distribution on complementary DNA strands. Cytosine rich strands may utilize cytosine-cytosine base pairing to form a four-stranded structure known as the i-motif (iM). The stability of iMs is affected by several factors such as DNA sequence, temperature, pH, ionic strength of the solution, and crowded conditions. While the effects of temperature, pH, and crowding conditions on iM stability have been well documented, the effects of ion presence in a solution has been less studied. Hence, those studies are the basis …

Characterizing 3-O-Sulfation-Induced Novel Compact Topologies In Heparan Sulfate And Their Interactions With Proteins, Samuel Holmes

Theses and Dissertations

Heparan sulfate (HS) is highly-charged, linear polysaccharide that interacts with numerous proteins in humans as consituents of proteoglycans. The action of sulfotransferase enzymes during the biosynthesis of HS can generate a combinatorially massive library of differentially sulfated sequences. Furthermore, the number and position of these sulfate groups are key to their biological activity, modulating their selectivities for certain proteins at the cell surface or ECM. The installation of a sulfate on the C3 hydroxyl of a glucosamine residue in HS represents the rarest of the sulfations, despite the HS 3-O-sulfotransferase (3OST) family being the most diverse of the other sulfotransferases. …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

The Effects Of Tubulin Post-Translational Modifications On The Flagellar Motility Of Trypanosoma Brucei, Katherine Wentworth

All Theses

Trypanosoma brucei is a parasitic kinetoplastid that causes African trypanosomiasis and is transmitted to a mammalian host by the tsetse fly (Glossina spp.). T. brucei relies on its flagellar motility to carry out its morphological changes from the procyclic form (predominant in the fly vector) to the bloodstream form (infectious form in mammals) and navigate the bloodstream of its host. The driving structure within the flagellum is the axoneme, which is composed of microtubules and dynein motor proteins. The tubulin code hypothesis suggests that cells regulate microtubule motor protein activity through post-translational modifications (PTMs) of alpha and beta …

Conformation Of The U12-U6atac Snrna Complex Of The Minor Spliceosome And Binding By Ntc-Related Protein Rbm22, Joanna Ciavarella

Dissertations, Theses, and Capstone Projects

Splicing of precursor messenger (pre-m)RNA is a critical process in eukaryotes in which the non-coding regions, called introns, are removed and coding regions, or exons, are ligated to form a mature mRNA. This process is catalyzed by the spliceosome, a multi-mega Dalton ribonucleoprotein complex assembled from five small nuclear ribonucleoproteins (snRNP) in the form of small nuclear (sn)RNA-protein complexes (U1, U2, U4, U5 and U6) and >100 proteins. snRNA components catalyze the two transesterification reactions while proteins perform critical roles in assembly and rearrangement. U2 and U6 snRNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA. …

Atg23 Dimerization Drives Membrane Tethering In Yeast Autophagy, Kelsie A. Leary

Dartmouth College Ph.D Dissertations

All cells undergo stress throughout their lifetime, including single-celled bacterium or a single cell from a plant or a human. This stress can result in damage that can be detrimental to the cell if it is not removed. Thus, healthy cells require a tight balance between clearing damaged cellular material and its replenishment. Autophagy is a highly conserved process evolved by cells to encapsulate damaged material in a double membrane vesicle for its delivery to the lysosome (in mammals) or the vacuole (in yeast). Upon lysosomal delivery, the contents are degraded and returned to the cell for reuse. Autophagy can …