Biochemistry, Biophysics, and Structural Biology Commons^™

Positron Emission Tomography In Oncology And Environmental Science, Samantha Delaney

Dissertations, Theses, and Capstone Projects

The last half century has played witness to the onset of molecular imaging for the clinical assessment of physiological targets. While several medical imaging modalities allow for the visualization of the functional and anatomical properties of humans and living systems, few offer accurate quantitation and the ability to detect biochemical processes with low-administered drug mass doses. This limits how physicians and scientists may diagnose and treat medical issues, such as cancer, disease, and foreign agents.

A promising alternative to extant invasive procedures and suboptimal imaging modalities to assess the nature of a biological environment is the use of positron emission …

Integrating In Vitro And In Silico Approaches To Gain Insight Into The Mechanism Of Amyloid Fibrillogenesis, Marvin M. Bilog

Dissertations, Theses, and Capstone Projects

Amyloid fibril formation, the hallmark of numerous amyloid-related diseases, has been the subject of a vast number of scientific studies due to its pathological implications. Since the fibrillization process exhibits a certain level of intricacy, its investigation requires a multidisciplinary approach that integrates both experimental and computational methods. In vitro techniques involve biophysical assays and imaging tools for characterizing the structural and kinetic aspects of amyloid fibril formation. In parallel, in silico techniques offer programs for predicting atomistic details and behaviors of amyloidogenic proteins and peptides at the nanoscale level. Serum amyloid A (SAA), human islet amyloid polypeptide (hIAPP), and …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Exploring The Design Space Of Antifungal Peptides, Miryam Kikhwa

Seton Hall University Dissertations and Theses (ETDs)

The synthesis, characterization, and evaluation of antifungal activity of peptides FQ15 and FG10 will be conducted to address the hypothesis. The hypothesis of this thesis is that a peptide with similar properties to AS15 would have similar activity against Cryptococcus neoformans. This study addresses the challenge of drug- resistant microbes by developing inhibitors targeting lipid flippase and exploring their potential as antimicrobial agents against Cryptococcus neoformans. Chapter 1 provides a historical context of the background on the development of antimicrobials and common antifungal treatments, as well as an introduction about C. neoformans and its resistance mechanism. Chapter 2 introduces the …

The Interactions Of Centromeric Nucleosomes Elucidated By Atomic Force Microscopy, Shaun Filliaux

Theses & Dissertations

Nucleosomes are the fundamental unit of compaction for DNA in the genome. These positively charged proteins have two main types of nucleosomes: canonical (H3 containing) and centromere (CENP-A containing). The compacting of DNA allows for DNA to fit into the nucleus of cells, but creates a barrier for DNA accessibility for operations such as replication or transcription. Centromeric chromatin is a subset of chromatin structure and governs chromosome segregation. Compared to the bulk chromosome, centromeres are composed of H3 and CENP-A nucleosomes in which H3 histones is replaced by its homolog CENP-A histone. This results in nucleosomes with different structures, …

Characterizing The Role Of Pa5189 Of Pseudomonas Aeruginosa In Deletion And Overexpression Mutants, Seh Na Mellick

Theses/Capstones/Creative Projects

In the context of rising multidrug resistance in biofilm-forming pathogens like Pseudomonas aeruginosa, this study investigates the role of the understudied transcription factor PA5189 in antibiotic resistance and biofilm formation. PA5189 deletion and overexpression mutants were created in a parent P. aeruginosa strain using pEX18Tc-based recombinant suicide vectors, with genotypic verification of putative triparental conjugants achieved through restriction digestion and PCR. The study revealed that PA5189 overexpression significantly increases resistance to commonly used broad spectrum antibiotics such as ciprofloxacin and imipenem. Additionally, differential expression of PA5189 was found to notably affect biofilm formation, with variations contingent on the nutrient …

Establishing An Objective, Quantifiable Method For Detecting Erosive Tooth Wear, Camille Kita

Biological Sciences Undergraduate Honors Theses

This study aims to monitor and evaluate erosive tooth wear (ETW) by measurement of enamel surface thickness and texture in a clinical setting. The objective approach is fundamentally different from the standard subjective visual assessment that professionals in the dental field using the Basic Erosive Wear Evaluation (BEWE) method.

Twenty-nine hyposalivation and three control subjects were used in this longitudinal study, for a total of 597 samples (only 577 teeth were eligible for surface texture analysis) evaluated in a longitudinal study including both baseline and 12 month follow up surfaces. Each participant’s buccal surface of the tooth was first analyzed …

Cyanoacrylate Deposition Onto Sebum With Pretreatment Of Amine, Isaac Baltz

Chemistry & Biochemistry Undergraduate Honors Theses

Super glue, or ethyl cyanoacrylate, fuming is commonly used in forensic science to develop latent fingerprints on nonporous surfaces[7]. Fingerprints are primarily made up of the oily substance secreted by sebaceous glands better known as sebum. Previously it has been shown that exposure of fingerprints to diisopropylamine dramatically increases the deposition of cyanoacrylate polymers on the fingerprints[1]. However, the heterogeneity of any series of real fingerprints made it difficult to quantitatively assess this effect. This heterogeneity includes not just the amount of sebum but the presence of unknown amounts of proteins, amino acids, and other potential nucleophiles which catalyze the …

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 …

Understanding Taf13 (Tata Box-Binding Protein-Associated Factor 13) Upregulation In Eukaryotic Cells, Selin Kaplanoglu

Honors Theses

TATA-binding protein (TBP) and TBP-associated factors (Tafs) comprise RNA Polymerase II (RNA Pol II) pre-initiation complex. This universal component carefully controls the transcriptional initiation process. One of the Tafs, Taf13, also plays an important role in the regulation of RNA Pol II transcription initiation which is evolutionarily conserved from yeast to humans. It is found that Taf13 is overexpressed in cancer cells, although the exact mechanism that is responsible for this overexpression is unclear. Our hypothesis suggests that targeted degradation by the 26S proteasome via ubiquitylation [Ubiquitin-Proteasome System (UPS)] may be the mechanism that regulates the stability of Taf13. To …

The Contribution Of Micrornas To Rybp Silencing In Glioblastoma Multiforme, Alex B. Lee

Graduate Theses

Glioblastoma multiforme (GBM) is a highly aggressive and invasive tumor of the central nervous system (CNS). Survival rates are abysmal, with only 7.2% of patients alive 5-years after diagnosis. Because of this, understanding epigenetic alterations that give GBM tumors their aggressive phenotypes is critical for the development of more targeted and effective therapies. These alterations frequently affect a group of proteins called the Polycomb group proteins, which play important oncogenic and tumor suppressive roles in cancer. One Polycomb protein, the RING1- and YY1-binding protein (RYBP), is downregulated in a majority of GBM patients, suggesting a strong tumor suppressive property. In …

Molecular Characterization Of Stress Response In Western Honey Bee (Apis Mellifera), Faizan Tahir

Master's Theses

Honey bees are incredibly important for the reproduction of flowering plants and the sustainability of agricultural ecosystems. However, they face various stressors such as pesticides, pathogens, habitat loss, and climate change. Extensive research has been conducted to understand how bees respond to these stressors. Scientists have discovered that honey bees exhibit complex physiological and behavioral responses to stress at individual and colony levels. Stress can have a significant impact on their immune function, foraging behavior, and reproductive success (Decourtye et al., 2010). Understanding bee responses to stress is crucial for several reasons. Firstly, honey bees are vital for the pollination …

Identifying A Target Protein And Ligands For Autoimmune Disorders, Sarah Caruthers

Computational and Data Sciences (MS) Theses

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by unprovoked inflammatory responses that lead to tissue degradation. Patients suffering from SLE display an overexpression of master regulatory protein HIF-1 HIF-1is a transcription factor for pro-inflammatory cytokine interleukin-17A (IL-17A), which is highly involved in inflammatory reactions within the body. To search for a treatment for SLE, computer aided drug discovery techniques were utilized. The transcription factor complex for IL-17A was reconstructed through multiple protein docking techniques. The heteroprotein complex was profiled using 3D macromolecular visualization software and binding cavities within HIF-1 were calculated. Molecular docking simulations were run on the …

Intrinsically Disordered Proteins And Their Role In Biomolecular Condensates, Danielle Latham

All Dissertations

Proteins are biomacromolecules responsible for the functions of life. While classically proteins are thought to be well structured in order to perform a specific function, 50% of proteins within Eukaryotic cells contain intrinsically disordered regions (IDRs), regions with no well-defined structure. IDRs are often used for cell signaling, responding to external factors such as temperature changes or the presence of small molecules. To understand how IDRs can function without structure, it is important to understand the dynamics of such systems. Understanding IDR intramolecular and intermolecular interactions will shed light on IDR dynamics. Intramolecular interactions are first explored using fluorescence spectroscopy …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

Assessing Nordihydroguaiaretic Acid Properties And Its Potential Therapeutic Effect For Glioblastoma, Jose Arturo Guerrero

Open Access Theses & Dissertations

This study employs a combination of theoretical and experimental analysis to spectroscopically investigate the biomechanistic structure relationship and therapeutic effects of the Nordihydroguaiaretic Acid (NDGA) chemical derived from the Larrea Tridentata plant. These relationships are crucial for understanding NDGA's efficacy in disease prevention, treatment, and potential toxicological effects. While the medicinal and antiviral properties of the NDGA have been studied extensively, there remains a gap in optically identifying and reporting its structural changes. The current research successfully reveals evident trends in NDGA's vibrational signatures, particularly highlighting the absence of the Raman feature at 780 〖cm〗^(-1) as indicative of a fully …

Characterization Of The Androgen Receptor H1-H3 Loop As A Putative Fkbp Regulatory Surface, Isela Rodriguez

Open Access Theses & Dissertations

Prostate Cancer (PCa) is one of the most common life-threatening malignancies diagnosed among American men. Initiation and progression of PCa are dependent upon androgen receptor (AR) regulated genes. Functional receptor conformation is influenced by the cooperation of chaperone and cochaperone proteins including the 52 and 51 kDa FK506 binding proteins (FKBP52 and FKBP51). FKBP52 is known for being a positive regulator of AR, PR (progesterone receptor), and GR (glucocorticoid receptor) activity, whereas FKBP51 negatively regulates steroid hormone receptor activity. As a result, these two proteins have become highly promising therapeutic targets for the disruption of mechanisms important in several endocrine-related …

Investigating The Role Of Tryptophan In The Native Photo-Crosslinking Of A Cys-Containing Transmembrane Helix To A Membrane Lipid Double Bond, Michael Jay Telehany

Undergraduate Honors Theses

Our research group has previously discovered that a Cys residue within a transmembrane (TM) helix can directly photo-crosslink to a membrane lipid via an oxythiolation addition reaction to the double bond within the lipid, with a reaction yield of 10-20%. The pH-low Insertion Peptide (pHLIP) serves as our model TM helix, while the POPC lipid bilayer is our model membrane. We had long believed that the Trp residues within the sequence of pHLIP served as the key chromophore for this reaction, and thus they were essential for the formation of the TM helix-lipid adduct. To test this hypothesis, I synthesized …

Tools For Biomolecular Modeling And Simulation, Xin Yang

Mathematics Theses and Dissertations

Electrostatic interactions play a pivotal role in understanding biomolecular systems, influencing their structural stability and functional dynamics. The Poisson-Boltzmann (PB) equation, a prevalent implicit solvent model that treats the solvent as a continuum while describes the mobile ions using the Boltzmann distribution, has become a standard tool for detailed investigations into biomolecular electrostatics. There are two primary methodologies: grid-based finite difference or finite element methods and body-fitted boundary element methods. This dissertation focuses on developing fast and accurate PB solvers, leveraging both methodologies, to meet diverse scientific needs and overcome various obstacles in the field.

Characterization Of Rna Binding Proteins Regulating Axonal Localization Of Prenyl-Cdc42 Mrna, Ashley I. Loomis

Senior Theses

Following traumatic injury, axons in the peripheral nervous system (PNS) can spontaneously regenerate, albeit rather slowly. This regeneration requires messenger RNA (mRNA)-localization into and translation within the axons. One such mRNA originates from the CDC42 gene, which produces two mRNA splice variants: Prenyl-CDC42 and Palm-CDC42 encoding mRNAs. CDC42 promotes axon growth and regeneration by regulating actin filament polymerization in growth cones of axons. This plays an important role to support nerve regeneration in humans. The prenyl-Cdc42 mRNA is found in both central nervous system (CNS) and PNS axons, where it can be locally translated into CDC42 protein, which is subsequently …

Multi-Scale Simulations Of Dynamic Protein Structures And Interactions, Yumeng Zhang

Doctoral Dissertations

Intrinsically disordered proteins (IDPs) are functional proteins that lack stable tertiary structures in the unbound state. They frequently remain dynamic even within specific complexes and assemblies. IDPs are major components of cellular regulatory networks and have been associated with cancers, diabetes, neurodegenerative diseases, and other human diseases. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for mechanistic understanding of IDPs in biology, diseases, and therapeutics. However, accurate simulation of the heterogeneous ensembles and dynamic interactions of IDPs is extremely challenging because of both the prohibitive computational cost and demanding force field …

High Resolution Mass Spectrometry As A Platform For The Analysis Of Polyoxometalates, Their Solution Phase Dynamics, And Their Biological Interactions., Daniel T. Favre

Doctoral Dissertations

Polyoxometalates (POMs) are a class of inorganic molecule of increasing interest to the inorganic, bioinorganic and catalytic communities among many others. While their prevalence in research has increased, tools and methodologies for the analysis of their fundamental characteristics still need further development. Decavanadate (V10) specifically has been postulated to have several unique properties that have not been confirmed independently. Mass spectrometry (MS) and its ability to determine the composition of solution phase species by both mass and charge is uniquely well suited to the analysis of POMs. In this work we utilized high-resolution mass spectrometry to characterize V10 in aqueous …

The Impact Of A Non-Ionic Adjuvant To The Persistence Of Pesticides On Produce Surfaces, Daniel Barnes

Masters Theses

Adjuvants can enhance the performance of the pesticide active ingredients in many ways including decreasing surface tension and reducing evaporation. Understanding how adjuvants effect pesticide behavior (e.g., surface persistence) is crucial for developing effective pesticide formulations, as well as facilitating the development of effective approaches to reduce pesticide residues from the surface of fresh produce post-harvest. The objective of this study is to investigate the effect of a non-ionic surfactant, Surf-Ac 910, on the persistence of two model pesticides, thiabendazole and phosmet on apple surfaces. The result shows that the addition of Surf-Ac 910 increased both the maximum wetted area …

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …

Development Of An Integrated Workflow For Nucleosome Modeling And Simulations, Ran Sun

Doctoral Dissertations

Nucleosomes are the building blocks of eukaryotic genomes and thus fundamental to to all genetic processes. Any protein or drug that binds DNA must either cooperate or compete with nucleosomes. Given that a nucleosome contains 147 base pairs of DNA, there are approximately 4^147 or 10^88 possible sequences for a single nucleosome. Exhaustive studies are not possible. However, genome wide association studies can identify individual nucleosomes of interest to a specific mechanism, and today's supercomputers enable comparative simulation studies of 10s to 100s of nucleosomes. The goal of this thesis is to develop and present and end-to-end workflow that serves …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Comparative Animal Mucomics, Antonio R. Cerullo

Dissertations, Theses, and Capstone Projects

Mucus is one of Nature’s most abundant and versatile biomaterials. These secretions are present in all animals, from the lowly garden snail to the great blue whale, and fulfill a multitude of functions, acting as antimicrobial barriers, moisturizers, adhesive glues, surface lubricants, and mineralizing agents. Despite their importance, very little is known about mucus compositions or properties. The largest challenge precluding the greater understanding of mucus function is its complexity; a single mucus contains complex mixtures of proteins, glycans, and ions that all have important roles in function. Therefore, understanding mucus function necessitates analysis that compares different mucus from one …

Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave

Dissertations, Theses, and Capstone Projects

The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …

The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis

Theses and Dissertations

The underlying etiology of numerous disease states results from perturbations in the maintenance of cellular proteostasis. Carcinogenesis relies on these perturbations to foster uncontrolled cell growth and eventual metastases, while neurodegenerative diseases are a consequence of such perturbations. Control of these processes occurs at numerous molecular levels, commonly starting with transcription. A key transcriptional complex that is involved is the CDK8 Kinase Module (CKM). The CKM is conserved from yeast to man, forming a tetrameric complex consisting of MED12, MED13, CDK8, and CCNC. The CKM has not only been implicated in a variety of cancers but also in a spectrum …

Elastin-Like Polypeptide As A Model To Study Intrinsically Disordered Proteins, Sadegh Majdi

Theses and Dissertations

The elastin-like polypeptide (ELP) is a well-studied structural protein that is easily amenable to amino acid (AA) sequence modifications and has the potential to yield a wide variety of uses in bioengineering and biomedical applications. One unique property of ELP is the inclusion of intrinsically disordered domains (IDP) within the structure that allow for its diversity of physical properties. While it is generally understood that amino acid sequence dictates protein folding arrangements, the contributions of specific amino acid sequences to the intrinsic disorder of ELP has yet to be fully resolved. Therefore, identifying the contributions of specific amino acid sequences …