Biochemistry, Biophysics, and Structural Biology Commons^™

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 …

Can Biology Define A Human Life?, Katelyn De Leon

Regis University Student Publications (comprehensive collection)

I grew up contemplating the concept of life. From my Catholic grandmother to my pediatrician mother, I always received mixed perspectives on the hot topics of abortions, vaccines, and embryo use. I found that the controversy lies in an ambiguous, mixed understanding of what constitutes a human life. From biochemical approaches to extraterrestrial life forms and spirituality there is no clear, coherent all-encompassing definition of life. However, that does not mean we can merely agree to disagree. The concept of a human life has drastic implications on our everyday lives. An insufficient definition has, and will continue to, diminish quality …

Assessing Lipid Composition Of Cell Membrane In Escherichia Coli Under Aerobic And Anaerobic Conditions, Isabelle Johnson

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Escherichia coli is a highly studied model organism that is tightly tied to the mammalian gastrointestinal system. This microorganism has the capability to be a beneficial gut microbe or a life-threatening pathogen. In this study, the lipid membrane of Escherichia coli was investigated using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) to observe the change in its composition in aerobic and anaerobic conditions. Evidence of desaturation was discovered in the spectra, though more investigation is needed to understand the metabolic processes and drives that result in this change. Elucidation of these pathways in the future could result in …

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

All Dissertations

The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …

Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi

Graduate Theses and Dissertations

Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and …

Characterization Of Human Fibroblast Growth Factor 2 Variant To Determine Effects On Structure, Stability, And Cell Proliferation, Ryan Layes

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are a family of cell signaling proteins conserved across multiple species. Each individual FGF elicits different cellular functions including, but not limited to, proliferation, migration, differentiation, angiogenesis, and wound healing. One of the most studied members, fibroblast growth factor 2 (FGF2), has demonstrated substantial wound healing capacity in a wide range of tissues including skeletal, muscular, neural, respiratory, epithelial, and cardiovascular. This ability makes FGF2 a potential therapeutic for a wide range of conditions and injuries. However, due to a short half-life at room temperature, therapeutic use of FGF2 is limited. It has been demonstrated that …

Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff

Doctoral Dissertations

The endoplasmic reticulum (ER) is a large, multifunctional organelle that acts as the entrance into the secretory pathway, which accounts for the folding and maturation of approximately one third of the human proteome. It is the largest organelle in most cell types and is comprised of a single lumen and a contiguous membrane. The ER is responsible for a multitude of roles including protein translocation, folding, maturation, quality control, and glycosylation to name a few. These processes are buoyed by a large collection of chaperones and cochaperones, the largest subfamily of which is characterized by the presence of tetratricopeptide repeat …

Caulobacter Clpxp Adaptor Popa’S Domain Interactions In The Adaptor Hierarchy Of Ctra Degradation, Thomas P. Scudder

Masters Theses

The degradation and recycling of protein is a process essential for the maintenance and regulation of cellular function. More specifically, in Caulobacter crescentus, the ClpXP protease is responsible for driving progression through the cell cycle and protein quality control. This protease utilizes three known adaptors to selectively degrade proteins that initiate different stages of development. This thesis will elaborate on the specific binding interface on one of these adaptors, PopA, with another, RcdA, and focus in on specific residues on PopA and investigate their roles in adaptor binding and delivery of CtrA, the master regulator of Caulobacter. Finally, I …

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …

Endothelial Interleukin-17 Receptor D (Il17rd) Promotes Western Diet-Induced Aortic Myeloid Cell Infiltration, Shivangi Pande

Electronic Theses and Dissertations

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor), belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent monocyte adhesion. We utilized primary human aortic endothelial cells and demonstrated that RNAi targeting of IL17RD suppressed transcript levels by 83% compared to non-targeted controls. Further, RNAi knockdown of IL17RD decreased the adhesion of THP-1 cells …

A Quantitative Visualization Tool For The Assessment Of Mammographic Risky Dense Tissue Types, Margaret R. Mccarthy

Electronic Theses and Dissertations

Breast cancer is the second most occurring cancer type and is ranked fifth in terms of mortality. X-ray mammography is the most common methodology of breast imaging and can show radiographic signs of cancer, such as masses and calcifcations. From these mammograms, radiologists can also assess breast density, which is a known cancer risk factor. However, since not all dense tissue is cancer-prone, we hypothesize that dense tissue can be segregated into healthy vs. risky subtypes. We propose that risky dense tissue is associated with tissue microenvironment disorganization, which can be quantified via a computational characterization of the whole breast …

Dynamics Of Site Search Process And Formation Of Synaptosome Assembly Characterized By Single Molecule Approaches, Sridhar Vemulapalli

Theses & Dissertations

Genome dynamics and integrity are the two crucial features defining the successful functioning of cells and their maintenance and evolution. The genetic processes in the cell require distant communications between the regulatory regions controlled by specific proteins. Mistakes in this interaction process will lead to termination of the genetic process may lead to the cell damage, disease development or the cell death. Similar distant regulatory process is required for numerous genome integration systems such as Variable Diversity Joining (V(D)J) recombination system resulting in the specificity of the immunoresponse, a defining property of the adaptive immune system. A common feature of …

Selective Activation Of Thrombin Activatable Fibrinolysis Inhibitor (Tafi) Attenuates Metastatic And Angiogenic Capabilities Of Melanoma And Lung Carcinoma In Vitro, Jacklyn Krizsan

Electronic Thesis and Dissertation Repository

Metastasis and angiogenesis are hallmarks of aggressive cancers, both depending on degradation of extracellular matrix by proteases such as plasmin. Plasmin activation is inhibited by thrombin-activatable fibrinolysis inhibitor (TAFI)-mediated cleavage of terminal lysine residues on plasminogen receptors. Activation of TAFI is most effectively done in complex with thrombomodulin (TM). TM is known to have anti-cancer properties, but it is not known if this is due to TAFI activation or an alternative substrate protein C (PC). We hypothesize that specific promotion of TAFI activation with TM treatment will attenuate metastatic and angiogenic capabilities of tumour cells.

Melanoma and lung carcinoma cells …

Elucidating The Biomechanics Of Mertk-Mediated Efferocytosis, Brandon Hayato Dickson

Electronic Thesis and Dissertation Repository

Macrophages are key mediators of efferocytosis – the phagocytic engulfment and removal of apoptotic cells. During engulfment, the coordinated activity of efferocytic receptors induces the remodeling of the actin cytoskeleton, which facilitates the envelopment of the cell by the plasma membrane. Mer receptor tyrosine kinase (MERTK) is a crucial efferocytic receptor, but its role during actin remodeling is not well understood. Previously, our lab showed that MERTK is an activator of β₂ integrins – which are comprised of receptors known to induce the actin polymerization that is required for engulfment. We hypothesized that MERTK is an indirect stimulator of …

Proteomic Approaches To Identify Unique And Shared Substrates Among Kinase Family Members, Charles Lincoln Howarth

Dartmouth College Ph.D Dissertations

Protein phosphorylation is a reversible post-translational modification that is a critical component of almost all signaling pathways. Kinases regulate substrate proteins through phosphorylation, and nearly all proteins are phosphorylated to some extent. Crucially, breakdown in phosphorylation signaling is an underlying factor in many diseases, including cancer. Understanding how phosphorylation signaling mediates cellular pathways is crucial for understanding cell biology and human disease.

Targeted protein degradation (TPD) is a strategy to rapidly deplete a protein of interest (POI) and is applicable to any gene that is amenable to CRISPR-Cas9 editing. One TPD approach is the auxin-inducible degron (AID) system, which relies …

Functional Analysis Of The Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha-1 (Gabra1) Gene During Zebrafish Development., Nayeli Gabriela Reyes-Nava

Open Access Theses & Dissertations

The GABRA1 gene encodes for the alpha-1 (α1) subunit of the Gamma-Aminobutyric acid type A receptor (GABAAR), which are the primary modulators of synaptic inhibition in the central nervous system (CNS). Alpha-1 subunits are essential for maintaining the normal function of native receptors and contribute to over 60% of all GABAARs in the CNS. Remarkably, a broad spectrum of neurodevelopmental and epilepsy-associated disorders have been linked with mutations in the GABRA1 gene. However, the developmental, behavioral, and molecular mechanisms underlying GABRA1-associated epileptic disorders remain to be fully understood. Hence, the overarching goal of this dissertation is to investigate the behavioral …

Regulation Of The Wnt/Wingless Receptor Lrp6/Arrow By The Deubiquitylating Complex Usp46, Zachary T. Spencer

Dartmouth College Ph.D Dissertations

The evolutionarily conserved Wnt/Wingless signal transduction pathway is critical for the proper development of all animals and implicated in numerous diseases in adulthood. Upon binding of the Wnt/Wingless ligand, a cascade of events culminates in inactivation of the destruction complex, a negative regulator of the pathway, and the subsequent formation of singalosomes which mediate pathway activation. A critical component of signalosome formation is the Wnt/Wingless receptor LRP6/Arrow. Upon canonical pathway activation, LRP6/Arrow undergoes activation via phosphorylation by several kinases and complexes with another Wnt/Wingless receptor Frizzled, along with several cytoplasmic components. While many studies have investigated the regulatory mechanisms of …

Exploring Strain Variation And Bacteriophage Predation In The Gut Microbiome Of Ciona Robusta, Celine Grace F. Atkinson

USF Tampa Graduate Theses and Dissertations

Current microbiome studies have shown that the maintenance of homeostasis betweenmicrobial populations (e.g. bacteria, viruses) and the host immune system (e.g. innate immune molecules) is necessary for balancing health and disease outcomes within the host. These studies most often utilize vertebrate models; however, research in this field can benefit from diverse model systems that facilitate our ability to conduct experiments to identify phylogenically conserved rules influencing homeostasis in the gut of animals. The Dishaw has developed the use of a filter-feeding marine invertebrate chordate, Ciona robusta, to model such fundamental interactions[1]–[6]. While most biological diversity and functional contribution within microbiomes …

A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer

USF Tampa Graduate Theses and Dissertations

Lymphedema is a disease that occurs when lymph flow is impaired, resulting in tissue swelling, fibrosis, chronic inflammation and recurrent secondary infections. Lymphatic valves play a critical role in maintaining unidirectional lymph flow and evidence for valve defects have been reported in lymphedema patients. The lack of drugs that can correct lymphatic valve defects warrants a better understanding of the molecular regulators of lymphatic valve development and maintenance. Lymphatic valves first develop during embryogenesis in response to mechanotransduction signaling pathways triggered by oscillatory lymph flow. Since eNOS (gene name: Nos3) is a well characterized mechanotransduction signaling molecule in blood vessels, …

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

The Protective Effects Of Anthocyanins On Neurons, Abigail Lynn

Pence-Boyce STEM Student Scholarship

Parkinson’s and Alzheimer’s are debilitating neurodegenerative diseases that are largely thought to be exacerbated, and perhaps even caused, by oxidative stress in and around neurons. At the same time, there has been increased research in the field of nutrition and how the foods we eat impact our short- and long-term health. These combined interests have resulted in fascinating studies that have found certain foods, namely plants, can have a variety of medicinal benefits.....The purpose of this study is to determine if plant extracts that have high levels of certain phytonutrients can increase the activity of cellular enzymes that reduce oxidative …

Migratory Material: Epigenetics & Weaving At The Us-Mexico Border, Valerie Navarrete

Masters Theses

Discourse often sutures the body shut, disallowing representations of identity to outgrow sociopolitical interests. This issue may originate from borders, but also from the unnamable pathology that generational colonial trauma transmits to the mind, body, and environment. Without a direct form of translatability, this thesis proposes a new materialism that deviates from any object-oriented ontology. Untethered and intra-active, epigenetics and weaving represent objects that transform typical ways of knowing and seeing. Their sensitivity to the environment, in addition to their mobility across generations of time, broaden the spatiotemporal loci of the body and its embodiment. Proposing new materials that expand …

Identifying The Temporal N-Linked Glycosylation Changes During Liver Disease Progression: From Liver Injury To End-Stage Liver Disease, Shaaron Ochoa-Rios

MUSC Theses and Dissertations

The high mortality rates of liver diseases and primary liver cancers can be attributed to the lack of screening and diagnostic strategies currently available for early detection. Non-alcoholic fatty liver disease (NAFLD) is an early stage of liver disease known to progress to a variety of pre-malignant and malignant conditions, like advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA). Based on the wide variety of diseases that NAFLD can progress to, strategies to understand and detect the progression of NAFLD are of great value. Core fucosylation of N-linked glycans has been demonstrated to be useful for the clinical diagnosis …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie

Dissertations and Theses

Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria are playing …

Review Of Biomedical Applications Of Cardiovascular Tissue Engineering, Natalie M. Howard

Honors College Theses

Tissue engineering can be defined as processes that aim to generate three-dimensional functional tissues in vitrothat have been favorably altered according to the structural, biochemical, electrophysiological, and biomechanical properties of the desired tissue before implantation into the human body. In relation to cardiac tissues, these properties would include the ability to conduct action potentials, withstand systolic pressure, permit sufficient O₂ and CO₂penetration, sufficient vascularization to supply nutrients for cellular activity, surface topology that enables cellular communication, and more. As heart diseases and instances of myocardial infarction continue to rise worldwide, there is an increasing need for …

Examining Transcriptional Regulators During Muscle Development In Drosophila Melanogaster, Chaamy Yapa

Student Theses and Dissertations

In Drosophila melanogaster embryos, a distinct approach to study the transcriptional regulation is to examine the larval somatic muscle development. Transcription factors are essential regulatory proteins that help to control gene expression and respond to signaling pathways and various cues. Today, there are at least twenty transcription factors that have been discovered to contribute to the development of the 30 distinct larval somatic muscles in each abdominal hemisegment of Drosophila melanogaster. Several studies have already been conducted on muscle regulatory transcription factors including midline and apterous. These transcription factors were shown to control the development of muscles through mutant …

Methyltransferase, Glucose Adaptation, And Import Complex In Trypanosoma Brucei, Emily Knight

All Dissertations

Trypanosoma brucei is a kinetoplastid parasite responsible for human African trypanosomiasis (HAT) and nagana, a livestock wasting disease, which both endemic to sub-Saharan Africa. Unique to kinetoplastids are the specialized peroxisomes, named glycosomes, which compartmentalize the first several steps of glycolysis and gluconeogenesis, nucleotide sugar biosynthesis, and many other metabolic processes. Kinetoplastids are unique in that they have a single mitochondrion. In this work, I present the first study into SET domain proteins in any kinetoplastid parasites. We have characterized a predicted SET domain protein, TbSETD3, that localizes to the mitochondrion and a depletion of the protein results in growth …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …