Biochemistry, Biophysics, and Structural Biology Commons^™

A Look At Gene Control: Tracking The Ccnd1 Gene, Bryan Anders

Mahurin Honors College Capstone Experience/Thesis Projects

Cancer occurs when the cell does not properly control its own cell cycle. It then replicates in an out of control fashion leading to the death of various organs and then the demise of the organism as a whole. As it seems to have always been a problem for cell-based life, certain safeguards against cancer have been evolved over time. One such method comes in the form of prevention via cyclin proteins, which are encoded from cyclin genes. The gene that is the focus of this research is the CCND1, or cyclin D1, gene that controls the progression through various …

Characterization Of The Dyrk1a Protein-Protein Interaction Network, Varsha Ananthapadmanabhan

Theses and Dissertations

Human Dual specificity tyrosine (Y)-Regulated Kinase 1A (DYRK1A) is a protein kinase encoded by a dosage-dependent gene. An extra copy of DYRK1A contributes to Down syndrome (DS) pathogenesis while loss of one allele causes severe mental retardation and autism. DYRK1A is involved in phosphorylation of several proteins that regulate cell cycle control and tumor suppression. However, the function and regulation of this kinase is not well understood and current knowledge does not fully explain dosage-dependent function of this important kinase. Our previous proteomic studies identified several novel DYRK1A interacting proteins including RNF169, FAM117B, TROAP, LZTS1, LZTS2 and DCAF7. In this …

The Role Of Manganese In Streptococcus Sanguinis, Tanya M. Puccio

Theses and Dissertations

Streptococcus sanguinis is primarily associated with oral health as a commensal bacterium. As an opportunistic pathogen, S. sanguinis is capable of colonizing heart valve vegetations, leading to the disease infective endocarditis. Previous studies from our lab have identified the high-affinity manganese transporter SsaACB as important for endocarditis virulence. The impact that manganese depletion has on S. sanguinis had never been evaluated and a secondary manganese transporter has not been identified. Thus, we employed the use of a fermentor to control large-scale growth over time and depleted manganese in an ΔssaACB mutant using a metal chelator, EDTA. The changes in …

Role Of Microrna-483 In Pancreatic Β-Cells, Jackson Waugh

Dissertations, Master's Theses and Master's Reports

Insulin is an essential hormone produced by β-cells in the pancreas. The release of insulin is tightly regulated in healthy people in order to control blood sugar level in our body. However, people with Type 2 Diabetes have insufficient insulin secretion from pancreatic β-cells, leaving to high blood sugar (hyperglycemia) and β-cell failure. microRNAs (miRNAs or miR) are newly discovered small regulatory molecules and have emerged as important regulator of cell growth, differentiation, and organ function. Altered miRNA function has been implicated in the pathogenesis of a variety of human disease, including diabetes. In this report, we focus on dissecting …

Investigation Of The Phenotypic Effect Of Mutating A Highly-Conserved Cysteine Residue In The Rna Polymerase Beta Prime Subunit Of E. Coli Rna Polymerase, Meg Dillingham

Mahurin Honors College Capstone Experience/Thesis Projects

All bacteria contain a multi-subunit RNA polymerase (RNAPs) that is essential for gene expression. Because of the centrality of these enzymes in cellular life, the structure and function of the various subunits is intensely studied. The primary sequence of the RNAP β’ subunit contains five cysteine residues that are highly conserved. Four of the cysteines coordinate a zinc atom and form the beta prime subunit zinc binding domain (ZBD). Mutation of any one of the ZBD cysteines is lethal to the cell. However, the role of the fifth residue (C58), which is located upstream of the ZBD cysteines, has not …

Epigenetic Implications In Inorganic Arsenic-Mediated Carcinogenesis, Meredith Eckstein

Theses and Dissertations--Molecular and Cellular Biochemistry

Chronic, low dose exposure to inorganic arsenic (iAs) is a public health concern throughout the world, contributing to the development of many diseases, including lung cancer. Several mechanisms for iAs-mediated carcinogenesis have been proposed, of which the production of reactive oxygen species and formation of chromosomal aberrations are the most studied. Another equally important, yet less studied mechanism is dysregulation of epigenetic marks. “Epigenetics” refers to changes that occur on the DNA and chromatin that do not alter base pair identity, but alter compaction, expression, and regulation of specific DNA sequences. There are several types of epigenetic marks including histone …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Investigating The Role Of Centromeric Repeats In Female Meiotic Drive, Jocelyn Crawford

CMC Senior Theses

Female meiotic drive is an unequal transmission of alleles that arises through the competition of paired chromosomes for inclusion in the egg, resulting in an increase in frequency of the driven alleles regardless of their effect on fitness of the individual. In Mimulus guttatus (monkeyflower) second filial generations, driven alleles display transmission advantages resulting in the virtual elimination of recessive homozygotes, while the equivalent lines lacking drive elements conform to traditional Mendelian segregation population ratios. Centromeres have been identified as mechanistic drive elements due to their role in chromosomal segregation during female meiosis, with Mimulus providing the best documented case …

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry …

Investigation Of Glutamate Carboxypeptidase Ii Roles In The Folate Cycle Dependent Reproduction And Development Of Caenorhabditis Elegans, Jessica M. Derham

Masters Theses

Glutamate Carboxypeptidase II (GCPII) is a transmembrane, zinc metallopeptidase that is expressed in a wide range of organisms, including roundworms, mice, and humans. In humans, GCPII is primarily expressed in the prostate, kidneys, small intestine, and central nervous system. Within the small intestine, the expected function of GCPII is to aid in the absorption of dietary folate from the intestinal lumen. GCPII cleaves excess glutamates from folate to yield monoglutamated folate which is then readily transported into the enterocyte. Folate can then be used through the one carbon metabolic cycle for the synthesis of nucleotides, conversion of homocysteine to methionine, …

Characterization Of The Tsc/Dyrk1a Interaction, Supriya Joshi

Theses and Dissertations

The Tuberous sclerosis complex (TSC) includes TSC1, TSC2 and the TBC1D7 subunits that together function as a principal inhibitor of the mTOR protein kinase complex 1 (mTORC1). mTORC1 is a master regulator of cell growth and proliferation that responds to signaling cues such as growth factors and nutrient availability. Proteomic studies in our lab revealed an interaction between the TSC subunits and DYRK1A, a ubiquitous protein kinase encoded by a gene located in the Down syndrome (DS) region on human chr21. In this study, we sought to validate the interaction of the TSC components with DYRK1A and to determine the …

A Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Neural Development In Mice, Hao Wu, Jing Zhou, Tianhui Zhu, Ivan Cohen, Jason Dictenberg

Publications and Research

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse …

Fggy Carbohydrate Kinase Domain Containing Is Induced During Skeletal Muscle Atrophy And Modulates Map Kinase And Akt Signaling, Anastasia L. Smith

UNF Graduate Theses and Dissertations

Skeletal muscle atrophy can result from a range of physiological conditions, including denervation, immobilization, hindlimb unweighting, and aging. To better characterize the molecular genetic events of atrophy, a microarray was performed using skeletal muscle isolated from mice after 3 and 14 days of denervation and compared to control muscle to identify novel atrophy-induced genes. The microarray revealed that FGGY carbohydrate kinase domain containing (Fggy) is expressed in skeletal muscle and is induced in response to denervation. Bioinformatic analysis of the Fggy gene locus revealed two validated alternative isoforms, that we have termed Fggy-L-552 and Fggy-S-387, which have distinct transcription initiation …

Peroxiredoxin 6 And Inflammation In Alzheimer's Disease, Jared Ferrell-Penniman

Biological Sciences Theses and Dissertations

Alzheimer’s disease (AD) is known for its debilitating symptoms and poor prognosis. However, despite intense research into neurodegenerative diseases, there are few therapies targeted at the underlying mechanisms of the disease. Oxidative stress (OS) and inflammation are cellular phenomena thought to be key to the progression of the disease. Critically, peroxiredoxin 6 (Prx6), an antioxidant protein with multiple functions, has been identified from mammalian studies as a potential regulator of both OS and inflammation that may have a specific effect on AD. This project seeks to elucidate the role of Prx6 in AD as well as the underlying mechanisms. Drosophila …

Simultaneous Delivery Of Crispr/Cas Complexes And Donor Dna Using Cell-Penetrating Peptide-Adaptors, Maria Mugure Mbugua

Master of Science in Chemical Sciences Theses

Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/CRISPR associated protein (Cas) complexes are becoming the preferred technique for genomic editing because of their precision, efficiency and accuracy. Prokaryotes naturally use CRISPR/Cas complexes to detect and eliminate foreign nucleic acids after infections. Cas proteins form complexes with RNA to cause double-stranded breaks (DSBs) in the invader’s sequence. Researchers are trying to use CRISPR complexes to treat many human diseases caused by these mutations. Research using CRISPR/Cas systems in the treatments of many of the genetic diseases has resulted in misfortunes (such as toxicity to the patient or new diseases) because of the method …

Multidrug Resistance Regulators Mara, Soxs, Rob, And Rama Repress Flagellar Gene Expression And Motility In Salmonella Enterica Serovar Typhimurium, Srinivas Thota, Lon Chubiz

Biology Department Faculty Works

Production of flagella is costly and subject to global multilayered regulation, which is reflected in the hierarchical control of flagellar production in many bacterial species. For Salmonella enterica serovar Typhimurium and its relatives, global regulation of flagellar production primarily occurs through the control of flhDC transcription and mRNA translation. In this study, the roles of the homologous multidrug resistance regulators MarA, SoxS, Rob, and RamA (constituting the mar-sox-rob regulon in S. Typhimurium) in regulating flagellar gene expression were explored. Each of these regulators was found to inhibit flagellar gene expression, production of flagella, and motility. To different degrees, repression via …

Investigating Growth Performance And Intestinal Barrier Integrity In Heat-Stressed Modern Broilers And Their Ancestor Jungle Fowl, Travis Tabler

Graduate Theses and Dissertations

Heat stress (HS) has a negative effect on poultry production sustainability due to its adverse consequence on bird welfare, health, growth, and mortality. Although modern broilers have greater gut mass and higher energy use efficiency than unselected birds, they are more vulnerable to HS that induces “leaky gut syndrome,” or increased intestinal permeability. The aim of the current study was to determine the effect of HS on growth performance and gut barrier integrity in three modern broiler lines and their ancestor the Jungle Fowl. Four chicken populations including Giant Jungle Fowl (JF), Athens Canadian Random Bred (ACRB), 1995 Arkansas Random …

Mechanisms And Consequences Of Myb Gene Activation In Salivary Gland Tumors, Candace Frerich

Biomedical Sciences ETDs

Salivary gland adenoid cystic carcinoma (ACC) is an aggressive tumor with a tendency to infiltrate surrounding nerves and metastasize to distant sites. The standard treatment often fails to control local tumor recurrence and distant metastases and no approved targeted therapeutic options exist for these tumors. The goal of our studies was to reveal the molecular mechanisms driving ACC tumor development and novel drug targets to improve patient morbidity and mortality.

We first analyzed clinical and RNA-sequencing (RNA-seq) data for 68 formalin-fixed paraffin-embedded (FFPE) ACC tumor samples and described previously unappreciated molecular heterogeneity that predicts patient outcome. The poor outcome subgroup …

Discovery Of Genomic Variations By Whole-Genome Resequencing Of The North American Araucana Chicken, Rooksana E. Noorai, Vijay Shankar, Nowlan H. Freese, Christopher M. Gregorski, Susan C. Chapman

Publications

Gallus gallus (chicken) is phenotypically diverse, with over 60 recognized breeds, among the myriad species within the Aves lineage. Domestic chickens have been under artificial selection by humans for thousands of years for agricultural purposes. The North American Araucana (NAA) breed arose as a cross between the Chilean “Collonocas” that laid blue eggs and was rumpless and the “Quetros” that had unusual tufts but with tail. NAAs were introduced from South America in the 1940s and have been kept as show birds by enthusiasts since then due to several distinctive traits: laying eggs with blue eggshells, characteristic ear-tufts, a pea …

Deepep: A Deep Learning Framework For Identifying Essential Proteins, Min Zeng, Min Li, Fang-Xiang Wu, Yaohang Li, Yi Pan

Computer Science Faculty Publications

Background: Essential proteins are crucial for cellular life and thus, identification of essential proteins is an important topic and a challenging problem for researchers. Recently lots of computational approaches have been proposed to handle this problem. However, traditional centrality methods cannot fully represent the topological features of biological networks. In addition, identifying essential proteins is an imbalanced learning problem; but few current shallow machine learning-based methods are designed to handle the imbalanced characteristics. Results: We develop DeepEP based on a deep learning framework that uses the node2vec technique, multi-scale convolutional neural networks and a sampling technique to identify essential proteins. …

Multiple Cytosolic Dna Sensors Bind Plasmid Dna After Transfection, Nina Semenova, Masa Bosnjak, Katarina Znidar, Maja Cemazar, Loree Heller

Bioelectrics Publications

Mammalian cells express a variety of nucleic acid sensors as one of the first lines of defense against infection. Despite extensive progress in the study of sensor signaling pathways during the last decade, the detailed mechanisms remain unclear. In our previous studies, we reported increased type I interferon expression and the upregulation of several proposed cytosolic DNA sensors after transfection of several tumor cell types with plasmid DNA (pDNA). In the present study, we sought to reveal the early events in the cytosolic sensing of this nucleic acid in a myoblast cell line. We demonstrated that DNA-dependent activator of interferon …

Acute Systemic Inflammatory Response To Lipopolysaccharide Stimulation In Pigs Divergently Selected For Residual Feed Intake, Haibo Liu, Kristina M. Feye, Yet T. Nguyen, Anoosh Rakhshandeh, Crystal L. Loving, Jack C. M. Sekkers, Nicholas K. Gabler, Christopher K. Tuggle

Mathematics & Statistics Faculty Publications

Background: It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs’ immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells.

Results: LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p= 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count …

Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall

Forum Lectures

The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance, …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Nitric Oxide Is Involved In Heavy Ion-Induced Non-Targeted Effects In Human Fibroblasts, Megumi Hada, Premkumar B. Saganti, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the …

Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago

Dissertations, Theses, and Capstone Projects

A variety of biological functions depend on actin organization. The organization of actin is tightly regulated by a plethora of extracellular and intracellular signaling, scaffolding, and actin-binding proteins. Dysfunctions in this regulation lead to immune diseases, increased susceptibility to pathogens, neurodegenerative diseases, developmental disorders, and cancer metastasis. A variety of actin-dependent processes, including cell motility, are regulated by several proteins of interest: Paxillin, a scaffolding protein; WASP, an actin nucleating protein; SCAR/WAVE, another WASP family actin nucleating protein; Talin, a cortex-to-membrane binding protein; Myosin II, an F-actin contracting motor protein; and Protein Kinase C, a protein kinase. D. discoideum cells …

Effective Statistical Energy Function Based Protein Un/Structure Prediction, Avdesh Mishra

LSU New Orleans Theses and Dissertations

Proteins are an important component of living organisms, composed of one or more polypeptide chains, each containing hundreds or even thousands of amino acids of 20 standard types. The structure of a protein from the sequence determines crucial functions of proteins such as initiating metabolic reactions, DNA replication, cell signaling, and transporting molecules. In the past, proteins were considered to always have a well-defined stable shape (structured proteins), however, it has recently been shown that there exist intrinsically disordered proteins (IDPs), which lack a fixed or ordered 3D structure, have dynamic characteristics and therefore, exist in multiple states. Based on …

Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber

Chemistry Student Work

INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting …

Characterization Of Human Dutpase, Shawna Marie Rotoli

Graduate School of Biomedical Sciences Theses and Dissertations

Deoxyuridine nucleotidyl transferase (dUTPase) is an enzyme found in all organisms that have thymine as a component of DNA. It catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate thus precluding the buildup of dUTP pools as well as providing the substrate, dUMP, for the de novo synthesis of thymidylate. In Homo sapiens, there are four isoforms: mitochondrial (mDut), nuclear (nDut), variant 3 and variant 4. This work is largely focused on nDut. Using structural and MS analyses of recombinant dUTPase constructs, an intermolecular disulfide bridge between cysteine-3 of each nDut monomer was discovered. It was found that these two …

Divergent Transcriptional Regulation Of Suppressors Of Cytokine Signaling Genes In Adipocytes, Paula Mota De Sa

LSU Doctoral Dissertations

The Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway transduces several signals crucial for development and homeostasis. Suppressors of cytokine signaling (SOCS) proteins control JAK-STAT signaling via a negative feedback loop. The transcription factor STAT5 is known to play a significant role in fat cell development and function, and several studies suggest that acetylation may affect STAT5 transcriptional activity. To test this hypothesis, we treated 3T3-L1 adipocytes with growth hormone (GH) to activate STAT5 in the presence or absence of histone deacetylase (HDAC) inhibitors. STAT5 acetylation levels were low in adipocytes and mostly unchanged by the …