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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 …

An Evolutionary Comparative Study Of Congenital Stationary Night Blindness-Associated Trpm1 Genetic Variants Of Uncertain Significance In Horses And Humans Utilizing Caenorhabditis Elegans, Gabrielle Davis

Theses

Congenital stationary night blindness (CSNB) is a heterogeneous collection of genetic diseases affecting the eyes and vision in horses and humans. Current research has implicated several genetic mutations impacting different genes involved in phototransduction and signal transmission, including TRPM1. In horses, genetic mutations in TRPM1 also result in a leopard spotting pattern or leopard complex. The goal of this study is to examine the potential impact of CSNB associated TRPM1 missense variants of uncertain significance (VUS). Previous research in Caenorhabditis elegans have revealed an orthologous TRPM1 gene known as gon-2 that allows for comparative studies. The evolutionary relationship of …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Vircy-Seq : A Protocol For Characterizing Viral Activity, Tyler James Dion

Legacy Theses & Dissertations (2009 - 2024)

The main purpose of pharmaceutical production is to produce safe effective medicine for patient use. In an effort to ensure patient safety constant surveillance for viruses takes place. The detection of a viral nucleic acid in a pharmaceutical production setting results in investigations to assess its infectious potential. This is an intensive, expensive process that entails many tests such as the observation of hemadsorption, cytopathic effects (CPE), and more. These tests are typically specific and only capture certain viruses, as factors like CPE can only be observed in some viral species. A new investigational method that is effective on all …

Towards More Complete Metagenomic Analyses Through Circularized Genomes And Conjugative Elements, Benjamin R. Joris

Electronic Thesis and Dissertation Repository

Advancements in sequencing technologies have revolutionized biological sciences and led to the emergence of a number of fields of research. One such field of research is metagenomics, which is the study of the genomic content of complex communities of bacteria. The goal of this thesis was to contribute computational methodology that can maximize the data generated in these studies and to apply these protocols human and environmental metagenomic samples.

Standard metagenomic analyses include a step for binning of assembled contigs, which has previously been shown to exclude mobile genetic elements, and I demonstrated that this phenomenon extends to all conjugative …

Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases, Mahesh Koirala

All Dissertations

Electrostatics plays an essential role in molecular biology. Modeling electrostatics in molecular biology is complicated due to the water phase, mobile ions, and irregularly shaped inhomogeneous biological macromolecules. This dissertation presents the popular DelPhi package that solves PBE and delivers the electrostatic potential distribution of biomolecules. We used the newly developed DelPhiForce steered Molecular Dynamics (DFMD) approach to model the binding of barstar to barnase and demonstrated that the first-principles method could also model the binding. This dissertation also reflects the use of existing computational approaches to model the effects of Single Amino Acid Variations (SAVs) to reveal molecular mechanisms …

Screening For Potential Therapeutic Targets Of Yb-1 Protein Using A Bioinformatics Approach, Omar Muneer Karkoutly

Theses and Dissertations

Treatment options for cancer are becoming much more limited due to the robust characteristics of cancer that allows them to rapidly develop drug resistance. This may be a result of cancer cells’ ability to switch between differentiated and undifferentiated states (plasticity). Diagnostic measurement and detection of cancer and its progression is essential for developing successful treatments. Specific cancer targets whose expressions are highly associated with increased incidence, risk, and spread of cancer therefore become perfect targets for therapeutic intervention. One such novel target that is still being studied is the Y-box binding protein 1 (YB-1), which …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations & Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Mucinomics: A Bioinformatic Analysis Of Snail Mucins, And Their Function, Maxwell B. Mcdermott

Theses and Dissertations

This thesis outlines the current research on secreted snail mucus, highlighting the potential of this biopolymer, and also demonstrates a research strategy to fulfill the unmet need of examining the hierarchical structures that lead to the enormous biological and chemical diversity of snail mucus genes.

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

Dissertations & Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology. In …

Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek

Electronic Theses and Dissertations

JC polyomavirus (JCPyV) is a human-specific pathogen that infects 50-80% of the population, and can cause a deadly, demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). In most of the population, JCPyV persistently infects the kidneys but during immunosuppression, it can reactivate and spread to the central nervous system (CNS), causing PML. In the CNS, JCPyV targets two cell types, astrocytes, and oligodendrocytes. Due to the hallmark pathology of oligodendrocyte lysis observed in disease, oligodendrocytes were thought to be the main cell type involved during JCPyV infection. However, recent evidence suggests that astrocytes are targeted by the virus and act …

Characterization Of Iron-Sulfur Cluster Biogenesis In Methanogenic Archaea, Thomas Modlin Deere

Graduate Theses and Dissertations

Iron-sulfur (Fe-S) clusters are among the oldest cofactors on the planet, used by proteins in almost all forms of life on Earth to carry out processes ranging from energy transfer to DNA replication. Among the organisms believed to use these Fe-S proteins more extensively than almost any others are the methanogens, an ancient lineage of archaeal microbes that produce methane as a required product of their metabolism. Methane, the primary component of commercial natural gas, is both a potent greenhouse gas and an important fossil fuel. It can also be renewably produced as a biofuel. Biogenic methane is almost entirely …

Circrev1 Expression In Triple-Negative Breast Cancer, Meagan P. Horton

USF Tampa Graduate Theses and Dissertations

Triple-negative breast cancer (TNBC) comprises only 24% of breast cancer cases, yet is the second leading cause of cancer mortality in women due to its aggressive nature (1). This increase in mortality is due to the lack of receptors for three targetable growth factors (HER2, progesterone, and estrogen receptors). Our previous studies have indicated that these cancers are highly dysregulated in respect to alternative splicing. Hence, we undertook a study aimed at identifying circular RNAs (circRNAs) generated from back-splicing events which were dysregulated in TNBC. We have identified a novel circRNA transcript, circular REV1 (circREV1), which is upregulated in our …

Simulation Of The Interaction Between Striated Muscle Unc-45 And Transcription Factor Gata-4, Drake Alexander Duncan

Electronic Theses and Dissertations

Striated Muscle UNC-45, also known as UNC-45b, is an important protein that acts as a chaperone for myosin in cardiac and skeletal muscles, binding to myosin at its C-terminal UCS domain and regulating its assembly into thick filaments and sarcomeric structures. The UCS domain contains a large loop that is believed to be the first point of interaction between myosin and UNC-45b. GATA-4 is an essential transcription factor that facilitates transcription of several genes in cardiac development, particularly alpha-heavy chain myosin in heart tissue. Recently, studies have shown that there is interaction of GATA-4 with UNC-45b and that GATA-4 binds …

A Test Of Rad Capture Sequencing On Ethanol-Preserved Centennial And Contemporary Specimens Of Philippine Fishes, Madeleine I. Kenton

Biological Sciences Theses & Dissertations

Understanding the relationship between ecological characteristics and genetic change in natural populations in different time scales can reveal how anthropogenic stressors affect natural populations and can improve the success of conservation strategies. The purpose of the Philippines Partnerships for International Research and Education (PIRE) project is to examine levels of genetic change between historical fish samples collected by the USS Albatross expedition in the early 1900s in the Philippines and contemporary populations collected at the same localities. This study tests genetic protocols to process historical and contemporary DNA for simultaneous comparison. Two DNA library preparation methods, single digest RADseq (“un-baited” …

Computational Analysis And Prediction Of Intrinsic Disorder And Intrinsic Disorder Functions In Proteins, Akila I. Katuwawala

Theses and Dissertations

COMPUTATIONAL ANALYSIS AND PREDICTION OF INTRINSIC DISORDER AND INTRINSIC DISORDER FUNCTIONS IN PROTEINS

By Akila Imesha Katuwawala

A dissertation submitted in partial fulfillment of the requirements for the degree of Engineering, Doctor of Philosophy with a concentration in Computer Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2021

Director: Lukasz Kurgan, Professor, Department of Computer Science

Proteins, as a fundamental class of biomolecules, have been studied from various perspectives over the past two centuries. The traditional notion is that proteins require fixed and stable three-dimensional structures to carry out biological functions. However, there is mounting evidence regarding a “special” class …

Factor Fiction? Identifying A Putative Toxoplasma Gondii Transcriptional Complex, Julia M. Paquette

Honors Theses and Capstones

Toxoplasma gondii is a highly prevalent protozoan parasite that is estimated to infect 30-50% of the global population, though there is no treatment for chronic infection and current treatments for acute infection may have serious side effects. Transcription is a tightly regulated process in T. gondii, allowing the parasite to successfully invade and replicate within host cells, and it is thus a promising avenue to study gene regulation and to investigate possible novel therapeutics. In our lab’s previous research, a TFIID-like complex was identified in T. gondii and found to be associated with the parasite specific bromodomain protein BDP3. …

Machine Learning And Bioinformatic Insights Into Key Enzymes For A Bio-Based Circular Economy, Japheth E. Gado

Theses and Dissertations--Chemical and Materials Engineering

The world is presently faced with a sustainability crisis; it is becoming increasingly difficult to meet the energy and material needs of a growing global population without depleting and polluting our planet. Greenhouse gases released from the continuous combustion of fossil fuels engender accelerated climate change, and plastic waste accumulates in the environment. There is need for a circular economy, where energy and materials are renewably derived from waste items, rather than by consuming limited resources. Deconstruction of the recalcitrant linkages in natural and synthetic polymers is crucial for a circular economy, as deconstructed monomers can be used to manufacture …

Development Of Computational Tools To Target Microrna, Luo Song

Dissertations & Theses (Open Access)

MicroRNAs (a.k.a, miRNAs) play an important role in disease development. However, few of their structures have been determined and structure-based computational methods remain challenging in accurately predicting their interactions with small molecules. To address this issue, my thesis is to develop integrated approaches to screening for novel inhibitors by targeting specific structure motifs in miRNAs. The project starts with implementing a tool to find potential miRNA targets with desired motifs. I combined both sequence information of miRNAs and known RNA structure data from Protein Data Bank (PDB) to predict the miRNA structure and identify the motif to target, then I …

New Methods For Deep Learning Based Real-Valued Inter-Residue Distance Prediction, Jacob Barger

Theses

Background: Much of the recent success in protein structure prediction has been a result of accurate protein contact prediction--a binary classification problem. Dozens of methods, built from various types of machine learning and deep learning algorithms, have been published over the last two decades for predicting contacts. Recently, many groups, including Google DeepMind, have demonstrated that reformulating the problem as a multi-class classification problem is a more promising direction to pursue. As an alternative approach, we recently proposed real-valued distance predictions, formulating the problem as a regression problem. The nuances of protein 3D structures make this formulation appropriate, allowing predictions …

Deciphering The Ck2-Dependent Phosphoproteome And Its Integration With Regulatory Ptm Networks, Teresa Nunez De Villavicencio Diaz

Electronic Thesis and Dissertation Repository

Protein functions are regulated by the post-translational addition of covalent modifications on certain amino acids. Depending on their distance within the 3-dimensional structure, addition/removal of individual post translational modifications (PTMs) can be impacted by others. This PTM interplay constitutes an essential regulatory mechanism that interconnects the molecular networks in the cell. Protein CK2, a clinically relevant acidophilic Ser/Thr kinase, may be responsible for 10-20% of the human phosphoproteome. Such estimates agree with the number of known substrates, which continues to expand. Furthermore, the demonstration that CK2 participates in hierarchical phosphorylation and has similar sequence determinants to caspases suggest extensive PTM …

Structural Analysis Of The Multifunctional Spoiie Regulatory Protein Of Clostridioides Difficile., Blythe Emily Bunkers

Graduate Theses and Dissertations

Clostridioides (formally Clostridium) difficile is a medically relevant pathogen pertinent to infectious disease research. C. difficile is distinctly known for its ability to produce two toxins, enterotoxin A and cytotoxin B, and the propensity to colonize the mammalian gastrointestinal tract. It is known that metabolism is tightly correlated with sporulation in endospore producers such as C. difficile, but an interesting and novel regulatory relationship found by the Ivey lab has yet to be understood. The relationship explored in this study is observed between the sporulation factor, SpoIIE, which represses expression of an ABC peptide transporter, app. In this study, two …

A Comparative Taxonomic And Diversity Study Of Litter-Associated Fungi In Northwest Arkansas Forests, Rajaa Abdulrazzaq Abbas Al Aanbagi

Graduate Theses and Dissertations

Fungi are taxonomically the most species-rich group of organisms on the earth, ecologically occupy distinctive niches and interact with diverse other organisms throughout their biogeographic distributions and functionally play key roles through their various lifestyles. Plant litter, in particular, is a keystone component in ecosystems and provides heterogeneous microhabitats for the often overlooked litter-decomposing fungi and other organisms on the floor of temperate deciduous forests. Litter fungi involve indirect interactions with the plant, soil and whole food web network. However, the community structure and functions of litter-associated fungi as well as patterns of species richness distributed across various litter microhabitats …

A Proteomic Analysis Of Corydoras Sterbai Secretions And Tissues, Erik Powell Wictor

University of the Pacific Theses and Dissertations

Defensive mechanisms vary widely in the animal kingdom ranging from physical defenses like spines to chemical defenses such as toxins. Toxins in these secretions and tissues can fluctuate from enzymes to lipids to uncharacterized chemicals. Next generation -omics technology and mass spectrometry are extremely important in analyzing these samples because of their ability to distinguish minute amounts of toxic substance within a complicated sample. The goal of this experiment was to look at secretions and tissues from Corydoras sterbai. All samples in this study were proteolyzed using a mixture of Trypsin and Lys-C, fractionated, and run through nanoLC-MS/MS analysis using …

Development Of A Computer Algorithm For Generation Of Primers For Nucleic Acid Sequence Based Amplification (Nasba), Rohit Karnati

Honors Undergraduate Theses

Nucleic acid sequence based amplification (NASBA) is a primer based isothermal method of RNA/DNA amplification. Currently, primer design for NASBA has been restricted to hand creating sequences of oligonucleotides that must follow a set of rules to be compatible for the amplification process. This process of hand-creating primers is prone to error and time intensive. The detection of mutants, post amplification, also offers a benefit in point of care scenarios and the design of hybridization probes for sequences in the region of amplification is also an erroneous and time intensive process. By creating a program to design primers and hybridization …

Of Donuts And Promo : In Silico Approaches To Identification Of Transcriptional Regulators Of Salivary Acinar Differentiation, Connor Cillian Duffy

Legacy Theses & Dissertations (2009 - 2024)

The salivary gland is an organ often taken for granted by most people. However, its proper function is essential for several everyday activities, such as speaking, swallowing, and tasting. As such, impaired salivary gland function, such as that caused by Sjögren’s Syndrome or radiotherapy for head and neck cancers, can lead to a significantly reduced quality of life. The cells that produce saliva in salivary glands are known as acinar cells, which arise from proacinar cells generated during embryonic development. As such, in studying the promoter regions of proacinar and acinar genes, it may be possible to identify common transcription …

Microbial Ecology Of South Florida Surface Waters: Examining The Potential For Anthropogenic Influences, Chase P. Donnelly

HCNSO Student Theses and Dissertations

South Florida contains one of the largest subtropical wetlands in the world, and yet not much is known about the microbes that live in these surface waters. These microbes play an important role in chemical cycling and maintaining good water quality for both human and ecosystem health. The hydrology of Florida’s surface waters is tightly regulated with the use of canal and levee systems run by the US Army Corps of Engineers and The South Florida Water Management District. These canals run through the Everglades, agriculture, and urban environments to control water levels in Lake Okeechobee, the Water Conservation Areas, …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer, Natalia Junqueira Sumi

USF Tampa Graduate Theses and Dissertations

Lung cancer is the second most common cancer type and is associated with high mortality rates. The survival rate for lung cancer patients has increased slowly in the last decade mainly as the result of the development of novel targeted and immune therapies. However, non-small cell lung cancer patients lacking known or actionable driver mutations and small cell lung cancer patients with recurrent disease are still in urgent need of new therapies. Drug repurposing is an efficient way to identify new therapies since it uses clinically relevant small molecule drugs. Determination of off-targets of small molecules is a novel approach …

Software For Sequence Analysis Of Variants In Functional Screening Libraries And Personalized Genome Files, Jacklyn Michelle Newsome

UNLV Theses, Dissertations, Professional Papers, and Capstones

Detailed knowledge of protein function is critical for both the study of protein interactions and the development of drugs which target specific proteins. Currently, there are few techniques that directly examine protein function. The techniques that are available are time consuming and can only address one variant of a protein at a time. Our laboratory has designed 3 high throughput protein function screens. We hypothesize that these will address this shortfall.

The first screen is the Chimeric Minimotif Decoy (CMD) Assay. For this screen, we constructed red fluorescent proteins with one or more C-terminal minimotifs. Minimotifs are short, contiguous amino …