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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Comparative Analysis Of Dna Isolation Methods For The Human Microbiome, Hannah Chatwin Jan 2019

Comparative Analysis Of Dna Isolation Methods For The Human Microbiome, Hannah Chatwin

Undergraduate Honors Theses

The human microbiome is made up of millions of microbes coexisting in and on us with involvement in health and disease. The exact mechanisms by which this occurs have yet to be fully elucidated. Due to high variability in the composition of each person’s microbiome, it requires large numbers of people to begin to identify some of these processes. A major road block to generating large data sets for analysis is the high cost of DNA isolation from large collections of phenotypically well-characterized human subjects. This study explores the possible application of an inexpensive alternative DNA isolation method utilizing ...


Nanoscale Stiffness Cues Influence Valvular Interstitial Cell Activation To Myofibroblasts, Michaela Wenning Jan 2019

Nanoscale Stiffness Cues Influence Valvular Interstitial Cell Activation To Myofibroblasts, Michaela Wenning

Undergraduate Honors Theses

Surgery is currently the primary treatment option for aortic valve stenosis (AVS) patients, many of whom are ineligible for surgery and are left untreated. AVS is progression is known to differ between males and females, and an understanding of sex-specific mechanisms of disease progression is imperative in developing accurate treatment options for men and women. The development of a nonsurgical therapy for AVS patients requires a deeper understanding of the molecular and cellular mechanisms of AVS progression. Currently, the role of calcium phosphate nanoparticles detected in the aortic valve during early stages of AVS in influencing disease progression and valvular ...


The Molecular Basis Of Rna Recognition And Transcriptional Regulation By Fus And Prc2, Xueyin Wang Aug 2018

The Molecular Basis Of Rna Recognition And Transcriptional Regulation By Fus And Prc2, Xueyin Wang

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

RNA and protein interact with each other in the cell nucleus to form RNP (ribonucleoprotein) complexes. These RNPs play key roles in various steps of gene expression. This thesis focuses on two nuclear RNA-binding proteins: Fused in Sarcoma (FUS) and Polycomb Repressive Complex 2 (PRC2).

The normal functions of FUS are not fully understood, but RNA binding has been suggested to be crucial for FUS function and many RNA targets have been identified. Yet the features of RNAs necessary for FUS binding had not been systematically characterized. FUS bound all five published RNA motifs and other RNAs tightly, including fragments ...


Host And Viral Molecular Patterns Relevant To Pathogenicity And Immunity, Alexander Christian Stabell Aug 2018

Host And Viral Molecular Patterns Relevant To Pathogenicity And Immunity, Alexander Christian Stabell

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Patterns in nature, many going unnoticed, are a defining characteristic of life. In this thesis, I will describe four studies that I have completed during my doctoral work. These will highlight how both host immune system and viral pathogens harness non-random biological patterns to aid in immunity or increase pathogenicity, respectively. Chapter 2 will describe the evolutionary history of a component of the primate innate immune system, Schlafen11, and its involvement in the defense against viruses. I attempt to show that Schlafen11 takes advantage of the pattern of non-optimal codon usage of HIV-1 transcripts in order to inhibit viral replication ...


Multimodal Recognition Of Diverse Peptides By The Sh2 Domains Of Plcγ1 And Sh2b1, Marissa A. Mckercher Feb 2018

Multimodal Recognition Of Diverse Peptides By The Sh2 Domains Of Plcγ1 And Sh2b1, Marissa A. Mckercher

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

SH2 domains recognize phosphotyrosine (pY)-containing peptide ligands and regulate a wide array of signaling events within receptor tyrosine kinase pathways. SH2 domains have individualized specificity for peptides, encoded in the amino acids neighboring the pY of the ligand. In contrast to this simple view of signaling specificity, high-throughput array studies have identified several SH2 domains capable of recognizing peptides containing chemically distinct amino acids at the positions neighboring the pY. For example, the C-terminal SH2 domain (PLCC) of phospholipase C-γ1 (PLCγ1) typically binds peptides containing small and hydrophobic amino acids adjacent to the pY, but can also recognize unexpected ...


Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson Feb 2018

Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Cargo proteins moving between organelles are transported by membrane-enclosed vesicles. Identifying the factors regulating vesicle-mediated transport remains a major challenge in mammalian cells. Here, we performed unbiased genome-wide CRISPR-Cas9 genetic screens to systematically dissect insulin-dependent translocation of glucose transporters (GLUTs), a classic vesicle transport pathway crucial to mammalian physiology. These screens identified known regulators of the pathway as well as a large number of unknown regulatory factors that we validated in secondary screens. The identified genes encode established or predicted factors involved in vesicle budding or fusion, cargo sorting, signal transduction, cell motility, and cellular metabolism, as well as proteins ...


Modeling And Designing Genetic Devices Using Transcriptional Interference In Escherichia Coli, Antoni Escalas Bordoy Jan 2018

Modeling And Designing Genetic Devices Using Transcriptional Interference In Escherichia Coli, Antoni Escalas Bordoy

Chemical & Biological Engineering Graduate Theses & Dissertations

Microorganisms inhabit every extreme location of our planet. In their journey through the ages, they have been able to incredibly adapt to a myriad of different environmental conditions. A key mechanism for their success has been their ability to respond to environmental and nutritional changes through regulatory programs primarily encoded at the transcriptional level. This adaptability to new environments is what encourages scientists to believe in engineering a biological revolution that will transform our lives due to its potential to result in innovative approaches for bioremediation, sustainable energy production, and biomedical therapies. This thesis explores the potential of the phenomenon ...


The Role Of Dynamics Within Bama, The Central Component Of The Bam Complex, Pamela Arden Doerner Barbour Jan 2018

The Role Of Dynamics Within Bama, The Central Component Of The Bam Complex, Pamela Arden Doerner Barbour

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

BamA is an essential component of the β-­‐barrel assembly machine that folds and inserts outer membrane proteins (OMPs) into the outer membrane of Gram-­‐negative bacteria. BamA is an OMP itself comprised of two domains, a soluble periplasmic N-­‐terminal domain consisting of five polypeptide transport associated (POTRA) repeats and a C-­‐terminal 16-­‐stranded β-­‐barrel domain. The mechanism of BamA is poorly understood but structural data suggests BamA is a dynamic protein with respect to the POTRA domains and barrel. The POTRA domains, numbered 1-5 from the N- to C- termini, can be divided into two sub-domains ...


Discrimination Of Ssrna By Pot1 And Identification Of A Novel Cype Aptamer Through An Optimized Rna Selex Protocol, Neil Ryan Lloyd Jan 2018

Discrimination Of Ssrna By Pot1 And Identification Of A Novel Cype Aptamer Through An Optimized Rna Selex Protocol, Neil Ryan Lloyd

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

Protein-ligand specificity forms the fundamental basis for many biological mechanisms with properly tuned binding being required for most biological processes. Aberrant interactions can result in consequences ranging from wasted cellular resources to disease pathologies and death. As such, characterizing interaction specificities is a critical step in understanding biological systems. In this thesis I have characterized the RNA-binding properties of the telomere protection protein Pot1, developed an optimized SELEX protocol to characterize RNA-binding by newly identified RNA-binding proteins, and expanded on the RNA-binding specificity of one of those proteins, the epigenetic regulator CypE.

High fidelity binding to ssDNA, but not ssRNA ...


Rna-Rna Interactions In Rnp Granule Assembly, Briana Nicole Van Treeck Jan 2018

Rna-Rna Interactions In Rnp Granule Assembly, Briana Nicole Van Treeck

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

Ribonucleoprotein (RNP) granules, which are composed of numerous RNAs and proteins, are ubiquitous features of eukaryotic cells. This thesis investigates the assembly mechanisms of P-bodies and stress granules, two cytoplasmic granules that rely on RNAs unengaged in translation to form. Previous studies in the field have focused on the roles of proteins, and specifically their intrinsically disordered regions (IDRs), in targeting components and driving granule assembly. However, domain analysis of four proteins illustrates that having an IDR is neither sufficient nor necessary for targeting to P-bodies. Although IDRs have been shown to be important in some contexts, these results suggest ...


Composition And Dynamics Of Stress Granules, Tyler Matheny Jan 2018

Composition And Dynamics Of Stress Granules, Tyler Matheny

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

Stress granules are non-membranous assemblies of RNA and protein that form during conditions in which translation initiation is limited. Stress granules are of interest due to their potential role in the regulation of gene expression and their relation to other cytoplasmic RNP granules, such as p-bodies, germ granules, and neuronal granules. Additionally, stress granules are related to pathological aggregates observed in neurodegenerative diseases since (1) they share many protein components with these aggregates and (2) mutations that promote stress granule assembly or inhibit their clearance are causative in neurodegenerative disease.

The goals of this thesis are (1) to understand the ...


Crispr-Assisted Interrogation And Engineering Of Metabolic Pathways, Marcelo Colika Bassalo Jan 2018

Crispr-Assisted Interrogation And Engineering Of Metabolic Pathways, Marcelo Colika Bassalo

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Since Mendel’s work established the basis of inheritance in the late 1800s, multiple decades of research characterized monogenic traits across all domains of life. Yet, we still have a fairly limited knowledge on the genotype behind the vast majority of phenotypes. It is now evident that discrete biological functions can rarely be linked to a single gene. Further, these multigenic traits are often interconnected via a sophisticated and robust metabolic and regulatory network, selected by evolution in order to optimally distribute resources. The complexity of these multigenic traits challenges traditional genetic tools, broadly limiting our capability to understand and ...


Skeletal Muscle Metabolism: From Tissue To Stem Cell, Katherine Elise Gadek Jan 2018

Skeletal Muscle Metabolism: From Tissue To Stem Cell, Katherine Elise Gadek

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Excessive circulating triglycerides due to reduction or loss of lipoprotein lipase (LPL) activity contribute to hypertriglyceridemia and increased risk for pancreatitis. The only gene therapy treatment for LPL deficiency decreases pancreatitis but minimally reduces hypertriglyceridemia. Synthesized in striated muscle and adipose tissue, LPL is then trafficked to blood vessel endothelial cells where it hydrolyzes triglycerides into free fatty acids. We conditionally knocked out LPL in differentiated striated muscle tissue lowering striated muscle LPL activity and causing hypertriglyceridemia. We crossed these LPL knockout mice with mice possessing a conditional avian retroviral receptor gene and infected mice with human LPL or mCherry ...


Targets And Functions Of The Microrna-200 Family In The Developing Skin And Hair Follicle, Jaimee Elizabeth Hoefert Jan 2018

Targets And Functions Of The Microrna-200 Family In The Developing Skin And Hair Follicle, Jaimee Elizabeth Hoefert

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The microRNA-200 (miR-200) family is well known for preventing epithelial-to-mesenchymal transition in cancer. However, the targets and functions of this family in normal epithelial tissues remain unclear. This five-member microRNA (miRNA) family also presents a unique platform for studying miRNA-mediated regulation, as they share two nearly-identical seed sequences. The results presented within this dissertation establish a role for these miRNAs in governing hair follicle morphogenesis and fine-tuning cell specification by regulating cell adhesion, polarity, and signaling pathways. By directly ligating miRNAs to their targeted mRNA regions, numerous miR-200 family targets are identified, many of which are involved ...


Functional Characterization Of Disease-Causing Mutations In Human Myosin Heavy Chain Genes, Carlos D. Vera Jan 2018

Functional Characterization Of Disease-Causing Mutations In Human Myosin Heavy Chain Genes, Carlos D. Vera

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Biophysical and biochemical imbalance of mechanisms relevant to muscle function, can result in morphological changes to the tissue. While the purpose of activities involving exercise is to modify the shape and size of skeletal muscle, and the length of these muscles allows wide ranges of stiffness and stretch to be applied, cardiac tissue is not meant to change much. However, stressful extrinsic factors (poor diet, chemotherapy, etc) or intrinsic factors like inherited mutations in muscle functioning genes can result in a myopathy or a disease of the muscle. In fact, another biological process that requires much compliance of many molecules ...


Novel Factors At Endoplasmic Reticulum-Endosome Contact Sites, Melissa J. Hoyer Jan 2018

Novel Factors At Endoplasmic Reticulum-Endosome Contact Sites, Melissa J. Hoyer

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The endoplasmic reticulum is the cell’s platform for protein and lipid synthesis. Not only does the ER perform these functions, but it also regulates other organelles through membrane contact sites. To better understand the functions of ER membrane contact sites (MCSs), we optimized tools to monitor contact sites and identify new proteins at these MCSs. We recently showed ER MCSs mark positions of the fission of other organelles. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to the endosome budding domains that form from the endosome body and undergo fission from ...


Investigating The Molecular Mechanism Of Glut4 Trafficking, Jessica Miller Jan 2018

Investigating The Molecular Mechanism Of Glut4 Trafficking, Jessica Miller

Undergraduate Honors Theses

The insulin-stimulated glucose transporter GLUT4 is essential to maintaining metabolic homeostasis in mammalian cells. Regulated trafficking of GLUT4 to and from the plasma membrane relies on a complex molecular mechanism integrating insulin signaling and vesicle transport. Understanding this pathway becomes increasingly crucial as Type II Diabetes, a disease characterized by insulin resistance, becomes more prevalent in the population. Despite decades of research, the molecular mechanism of GLUT4 trafficking is not yet fully understood. CRISPR-Cas9 allows for the ablation of individual genes so their role in GLUT4 trafficking can be investigated. A flow cytometry-based assay is used in this study to ...


Facilitated Binding Of High Mobility Group Box 1 And P53 In Transcriptional Regulation, Emma Steffer Jan 2018

Facilitated Binding Of High Mobility Group Box 1 And P53 In Transcriptional Regulation, Emma Steffer

Undergraduate Honors Theses

Transcription of mRNA is a very important and highly regulated processes necessary for the growth and viability of cells. Human p53 is a transcriptional activator that can act as a tumor suppressor by inducing cell cycle arrest and apoptosis. HMGB1 is an architectural protein that can bind and bend DNA to aid transcriptional regulation. This project investigated the potential for HMGB1 to facilitate DNA binding by p53. Various gel shift assays were performed to see if the addition of HMGB1 to reactions containing p53 and DNA would increase the amount of p53/DNA binding observed. On wild-type DNA containing two ...


Emergence Of New Metabolic Pathways In Escherichia Coli, Michael Kristofich Jan 2018

Emergence Of New Metabolic Pathways In Escherichia Coli, Michael Kristofich

Undergraduate Honors Theses

Catalytic promiscuity provides a starting point for the evolution of new enzymes. Taking this concept further, a series of promiscuous enzymes may assemble to form the basis of a new metabolic pathway (termed “serendipitous pathway”) that may emerge and become more efficient in adapting bacterial cells that require it to grow. The Copley lab at the University of Colorado at Boulder has been observing genetic changes that improve growth of Escherichia coli cells that lack the essential gene pdxB. These genetic changes are believed to improve the flux of metabolites through one or more serendipitous pathways that make up for ...


Investigations Of Interactions Between The Microtubule Binding Domain Of Centrosomal P4.1 Associated Protein And Polyglutamylated Microtubules, Caroline Rhoads Jan 2018

Investigations Of Interactions Between The Microtubule Binding Domain Of Centrosomal P4.1 Associated Protein And Polyglutamylated Microtubules, Caroline Rhoads

Undergraduate Honors Theses

Microtubules maintain particularly diverse and important functions within the cell despite being polymers made up of two highly conserved proteins: a- and b-tubulin. Some of these diverse roles are explained by the presence of post-translational modifications occurring on the C-terminal tail of tubulin proteins, primarily detyrosination, polyglutamylation and polyglycylation. Misregulation of C-terminal tail post-translational modifications are observed in disease phenotypes and may increase the risk of some forms of cancers; however, the role of these post-translational modifications is not well understood. Working towards a goal of designing in vivo methods to study specific post-translational modifications, this paper examines the specificity ...


Understanding Exportin-1 As An Anti-Cancer Target, Russell Thomas Burke Jan 2018

Understanding Exportin-1 As An Anti-Cancer Target, Russell Thomas Burke

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Exportin-1 is a promising new anti-cancer target for selective inhibitors of nuclear export (SINE) molecules. Selinexor is a first-in-class SINE molecule in clinical trials for a variety of different cancers. Selinexor and other SINE molecules covalently bind exportin-1 and prevent nuclear export of cargo proteins. Over 200 Exportin-1 protein cargoes have been identified, including p53, pRB, IκB, and BRCA1. While early clinical success with inhibitors of Exportin-1 has been observed, the molecular mechanisms of response are still being examined. Previous studies have shown a variety of cell cycle effects and cell death. Here we show that inhibition of Exportin-1 causes ...


Fibroblast Growth Factor Receptor Function In Muscle Stem Cells, Tashi Hackett Jan 2018

Fibroblast Growth Factor Receptor Function In Muscle Stem Cells, Tashi Hackett

Undergraduate Honors Theses

Skeletal muscle has a remarkable ability to regenerate itself following injury and this is reliant upon a group of stem cells known as muscle stem cells Muscle stem cell dysfunction contributes to variety of muscle wasting diseases and insights into mechanisms that regulate MuSC function could lead to new therapies and further our understanding of stem cell biology in general. Fibroblast Growth Factor 2 (FGF2) is a protein that regulates muscle stem cell behavior through stimulation of cell surface tyrosine receptor kinases known as Fibroblast Growth Factor Receptors (Jones, 2001). Activation of the receptors by FGF will induce intracellular signaling ...


Design And Synthesis Of Toll-Like Receptor 8 Inhibitors: Optimizing The Potential Drugs For Autoimmune Diseases, Kyoin Koo Jan 2018

Design And Synthesis Of Toll-Like Receptor 8 Inhibitors: Optimizing The Potential Drugs For Autoimmune Diseases, Kyoin Koo

Undergraduate Honors Theses

The first line of defense during infection relies on detecting the presence of pathogens and triggering pro-inflammatory responses by pattern recognition receptors (PRRs). Among PRRs, Toll-Like Receptors (TLRs) have been studied most extensively. TLRs are membrane receptors that recognize molecular patterns associated with pathogens and damaged cells to initiate immune responses. TLRs are good drug research targets because improper activation of TLRs has shown to be correlated with pathogenesis of various autoimmune diseases. TLR8 is an endogenous receptor that recognizes single-stranded RNA from viral infections. When TLR8 is improperly activated by self-RNAs, it can possibly lead to rheumatoid arthritis (RA ...


Alk-Eml4-Positive Cancers And Combination Therapy: Probing The Apoptotic Threshold, Teagan Glass Jan 2018

Alk-Eml4-Positive Cancers And Combination Therapy: Probing The Apoptotic Threshold, Teagan Glass

Undergraduate Honors Theses

Of all diseases currently being researched, lung cancer is one of the most pressing due to its worldwide prevalence and high incidence of fatality. More specifically, non-small cell lung cancers (NSCLC) harboring ALK-EML4 gene fusion mutations are of particular interest to researchers due to their widely documented capability of becoming resistant to specialized treatment, such as kinase inhibition. This project was initiated with the aim of using in vitro combination drug treatment to more efficaciously inhibit the growth and survival of H3122 cells, an ALK-EML4-positive NSCLC cell line. In this study, H3122 cells were subjected to combined ALK and histone ...


Toward A Mechanistic Understanding Of Outer Membrane Protein Biogenesis, Alex Hunt Hopkins Jan 2017

Toward A Mechanistic Understanding Of Outer Membrane Protein Biogenesis, Alex Hunt Hopkins

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

The outer membranes of Gram-negative bacteria are essential to their survival and have a unique asymmetric structure that features an outer leaflet of lipopolysaccharide. Bacterial outer membranes are populated by integral membrane proteins with amphipathic transmembrane β-barrel domains called outer membrane proteins (OMPs). OMPs are translated in the cytoplasm and translocated across the inner membrane and periplasm before being inserted into the outer membrane. The β-barrel Assembly Machine (BAM), a hetero-pentameric protein complex at the outer membrane, recognizes, folds, and releases OMPs into the membrane. However, the functional contributions of individual BAM subunits, the architecture of the BAM, and the ...


Disruption Of P53 Activated Transcription By A Rationally Designed Peptide, Benjamin Levi Allen Jan 2017

Disruption Of P53 Activated Transcription By A Rationally Designed Peptide, Benjamin Levi Allen

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

Transcription is a key checkpoint in regulating cell processes. The activity of RNA Pol II is modulated through a variety of mechanisms at various stages of transcription, and the Mediator complex is a central player in carrying out these changes. Mediator is a 1.2 MDa complex composed of 30 subunits. A primary function of Mediator is to bridge the activation domain of a transcription factor bound at an enhancer with Pol II and the general transcription factors at a promoter. Mediator is therefore a direct conduit for transcription factors to activate their target genes.

Chapter 2 describes the design ...


Role Of Non-Coding Genetic Risk Variation In Chrna5-Chrna3-Chrnab4 Cluster On Chromosome 15q21 In Addiction, Lung Cancer, Learning And Memory, Sonya Kostova Belimezova Jan 2017

Role Of Non-Coding Genetic Risk Variation In Chrna5-Chrna3-Chrnab4 Cluster On Chromosome 15q21 In Addiction, Lung Cancer, Learning And Memory, Sonya Kostova Belimezova

Integrative Physiology Graduate Theses & Dissertations

Modern large-scale genetic approaches like GWAS have allowed the identification of common genetic variations that contribute to the risk architecture of psychiatric disorders. Majority of such susceptibility variants are located in non-coding genomic regions spanning multiple genes. Multiple GWAS have linked certain polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15q21, encoding for the alpha5, alpha3 and beta4 subunits of the nicotinic acetylcholine receptors (nAChRs) respectively, with an increased risk for a variety of smoking and drug-related behaviors, lung cancer, COPD, and reduced levels of cognitive performance (in domains such as attention, response inhibition, and discriminative abilities). One of the ...


Transcriptional Regulation In Cancer-Driven Cellular Stress And Functional Specialization Of A Myosin Heavy Chain Protein, Myh7b, Veronica L. Dengler Jan 2017

Transcriptional Regulation In Cancer-Driven Cellular Stress And Functional Specialization Of A Myosin Heavy Chain Protein, Myh7b, Veronica L. Dengler

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Cancer is a disease of dysregulated gene expression in which many developmental programs are hijacked. One such program is the cellular response to hypoxia, or low oxygen stress. Hypoxia-inducible factors (HIF) govern the cell’s response to this stressor. While much is known about the transcriptional programs HIF directs, comparably little is known about the transcriptional regulation enabling the progression of this response. In the first two chapters of this thesis, I report on the current state of knowledge of the HIF transcriptional program and present new evidence for the role of the conserved coactivator, TIP60, on HIF1A, the primary ...


Host And Viral Molecular Patterns Relevant To Pathogenicity And Immunity, Alexander Christian Stabell Jan 2017

Host And Viral Molecular Patterns Relevant To Pathogenicity And Immunity, Alexander Christian Stabell

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Patterns in nature, many going unnoticed, are a defining characteristic of life. In this thesis, I will describe four studies that I have completed during my doctoral work. These will highlight how both host immune system and viral pathogens harness non-random biological patterns to aid in immunity or increase pathogenicity, respectively. Chapter 2 will describe the evolutionary history of a component of the primate innate immune system, Schlafen11, and its involvement in the defense against viruses. I attempt to show that Schlafen11 takes advantage of the pattern of non-optimal codon usage of HIV-1 transcripts in order to inhibit viral replication ...


Elucidating The Ligand-Specific Role Of Tetraspanin12 As An Essential Co-Activator In Norrin/Frizzled4 Signaling And Retinal Vascularization, Maria B. Lai Jan 2017

Elucidating The Ligand-Specific Role Of Tetraspanin12 As An Essential Co-Activator In Norrin/Frizzled4 Signaling And Retinal Vascularization, Maria B. Lai

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Genetic evidence indicates that specific combinations of accessory proteins and ligands mediate vascular Frizzled (FZD) signaling via beta-catenin in different CNS structures. Accessory proteins in FZD receptor complexes are thought to determine ligand-selectivity and signaling amplitude. In the retina, TSPAN12 is an essential co-activator in Norrin/FZD4 signaling to mediate angiogenesis. The genes encoding mediators of Norrin/FZD4 signaling are linked to familial exudative vitreoretinopathy (FEVR), an inherited retinal disease that can lead to blindness. Yet, the molecular function of TSPAN12 and the specific cell type in which TSPAN12 functions in the retina remains poorly understood. Here, I utilized binding ...