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Articles 1 - 30 of 282

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

Principles And Properties Of Rna Self-Assembly, Gabriel Tauber Jan 2019

Principles And Properties Of Rna Self-Assembly, Gabriel Tauber

Undergraduate Honors Theses

Ribonucleoprotein (RNP) granules are membraneless assemblies of condensed RNA and protein that form through multivalent interactions between the constituent components. Recently, RNA self-assembly has been shown to contribute to the formation of stress granules, which are RNP granules associated with the stress response and neurodegeneration. However, little is understood about the properties of self-assembled RNA. Here, I show that different RNA sequences can self- assemble into condensates with distinct material properties and partitioning preferences in vitro. Due to interactions that minimize surface free energy, RNA self-assembly can generate the spontaneous self-patterning of RNA assemblies. By reducing surface free energy, thereby ...


Effects Of H-Ras Disease Mutations On Binding To The Ras Binding Domain Of Pi3ky Measured By Micro-Scale Thermophoresis, Justin Martyr Jan 2019

Effects Of H-Ras Disease Mutations On Binding To The Ras Binding Domain Of Pi3ky Measured By Micro-Scale Thermophoresis, Justin Martyr

Undergraduate Honors Theses

H-Ras is a G-protein responsible for the activation of multiple signaling pathways that control cell growth. Our primary interest is examining its role in the regulation of the phosphoinositide-3-kinase (PI3K) signaling cascade, as H-Ras has been previously shown to recruit PI3K to the plasma membrane where this lipid kinase phosphorylates PIP2 to PIP3, a signal for cellular growth. The H-Ras-PI3K-PIP3 signaling pathway is known to be highly oncogenic, with constitutive activation of H-Ras leading to increased PIP3 production and cell growth. We hypothesize that disease-linked mutations on the binding interface between Ras and PI3K increase the ...


Developmental And Functional Analysis Of Scutes In The Armored Catfish Corydoras Aeneus, Emily Volk Jan 2019

Developmental And Functional Analysis Of Scutes In The Armored Catfish Corydoras Aeneus, Emily Volk

Undergraduate Honors Theses

Fish scales are specialized biological structures of current interest in innovative materials design because of the combination of protective function, flexibility, and light weight they offer. This study presents a developmental and functional investigation of a particular fish scale structure, the scutes (bony external plates) of the armored Bronze Corydoras Catfish (Corydoras aeneus). Scutes in this model fish species were analyzed via three complementary approaches. First, scutes were documented throughout fish development via high-quality microscope images. These images were subsequently used to inform fabrication of synthetic models to characterize the relationship between scute overlap and overall bending stiffness of scute ...


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 ...


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 ...


Computational Protein Design For Peptide-Directed Bioconjugation, Joseph Gabriel Plaks Jan 2019

Computational Protein Design For Peptide-Directed Bioconjugation, Joseph Gabriel Plaks

Chemical & Biological Engineering Graduate Theses & Dissertations

Proteins enable living organisms to perform many of their critical functions, having been applied over evolutionary time to solve problems of overwhelming diversity and complexity. Protein engineering seeks to deploy these versatile molecules in addressing problems of human concern and would benefit from innovations that improve protein utilization in unnatural environments as well as from increased predictive capability in protein design.

Bioconjugation facilitates the use of proteins in unnatural environments by permitting the attachment of molecules, such as polymers, that can modulate protein stability, solubility, and activity and by mediating protein immobilization. We initially explored this propensity of bioconjugation by ...


A Mutation In Cav2.1 Linked To A Severe Neurodevelopmental Disorder Impairs Channel Gating, Sidharth Tyagi Jan 2019

A Mutation In Cav2.1 Linked To A Severe Neurodevelopmental Disorder Impairs Channel Gating, Sidharth Tyagi

Integrative Physiology Graduate Theses & Dissertations

Ca2+ flux via voltage-gated Ca2+ channels is essential to the regulation of membrane excitability, neurotransmission, and a variety of intracellular signaling processes. CaV2.1 is the predominant Ca2+ channel present in the presynaptic terminals of both neuromuscular junctions and many central synapses. Point mutations in CaV2.1 can drastically alter channel gating and expression, and indeed have been linked to two paroxysmal disorders – Episodic Ataxia Type 2, and Familial Hemiplegic Migraine Type 1. With the novel whole-exome sequencing technique, mutations linked to a new class of more severe disorders have been found with phenotypes like Episodic Ataxia ...


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 ...


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 ...


A Genome-Wide Association Study Of Common Executive Functioning: Bioinformatic Analyses Of Gwas Summary Statistics, Evann Mitchell Jan 2018

A Genome-Wide Association Study Of Common Executive Functioning: Bioinformatic Analyses Of Gwas Summary Statistics, Evann Mitchell

Undergraduate Honors Theses

Executive functions (EFs) are a group of higher cognitive operations that direct lower-level processes to enable an individual to evaluate and carry out goal-directed behaviors. While EFs have been implicated in several complex cognitive abilities, there is one broad higher order construct that influences all EFs, common EF (cEF). While common EF is known to be heritable (i.e. under genetic influence), little is known about the underlying molecular mechanisms. Utilizing genome-wide association studies (GWAS) are an effective method for investigating the genetic basis of complex, polygenic traits, such as cEF, by identifying significantly associated SNPs and genes through a ...


Characterizing The Interaction Between The A-Repeat Region Of Xist And Sharp, Torey Averick Jan 2018

Characterizing The Interaction Between The A-Repeat Region Of Xist And Sharp, Torey Averick

Undergraduate Honors Theses

X-Chromosome silencing is a highly conserved process that is essential for proper gene dosage in female mammalian cells. In humans, the process is initiated early in embryonic development and will persist throughout the organism’s life. Improper gene dosage is manifest in disorders such as Down Syndrome, but in the context of X chromosome inactivation, it is fatal. The process occurs within the nucleus of cells, often on the nuclear lamina, and is facilitated by a long non-coding RNA called Xist. Xist, which stands for X-inactivation specific transcript, works together with a suite of proteins that are involved with and ...


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 ...


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 ...


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 ...


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 ...


Potential Synthesis Pathway For Redox-Active Dna Nucleoside, Nicole Broda Jan 2018

Potential Synthesis Pathway For Redox-Active Dna Nucleoside, Nicole Broda

Undergraduate Honors Theses

Science has failed those who die from the treatment of an illness rather than the illness itself. DNA nanomachines hold the promise of improving the site specificity of drug delivery, which can combat the toxicity of the drug to healthy cells and in turn, decrease unnecessary patient deaths due to treatment. We have found a novel synthesis pathway for a reversible redox- active nucleoside (n-nucleoside) that has the promise to be incorporated in and create redox- active DNA. Synthesis of 5’-deazalloxazine-ribonolactone was achieved via sodium hydride catalyzed glycosylation of 1-a-chloro-3,5-ditoluoyl-2-deoxy-D-ribose (5’,3’-protected-chloro- ribose). We were not able ...


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 ...


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 ...


Altering Parameters Of Crispr/Cas9 Mediated Genome Editing In Escherichia Coli Helps Identify Sources Of Variation In Editing Efficiency, Reilly G. Fankhauser Jan 2018

Altering Parameters Of Crispr/Cas9 Mediated Genome Editing In Escherichia Coli Helps Identify Sources Of Variation In Editing Efficiency, Reilly G. Fankhauser

Undergraduate Honors Theses

CRISPR/Cas9, originating from a bacterial immune system, has been identified as a powerful tool for genome modification (Jinek, et al., 2012). Historically, analyzing genotype-phenotype relationships have been limited by DNA synthesis and sequencing technology. Recent developments in genome editing (CRISPR/Cas9) coupled to improvements in synthesis and sequencing allows mapping these relationships at an entirely new scale. A technique novel to the Gill lab for genome modification that harnesses the CRISPR-Cas system is “CRISPR Enabled Trackable Genomic Engineering” or “CREATE” technology. CREATE technology is one such strategy for simultaneously making hundreds of thousands of single genomic edits, then tracking ...


Liquid Crystal Phases Of Rna Mononucleosides, Emily Hayden Jan 2018

Liquid Crystal Phases Of Rna Mononucleosides, Emily Hayden

Undergraduate Honors Theses

Deoxyribonucleic Acid (DNA) can form columnar liquid crystal phases in solutions of both short strand, base-pair oligomer solutions, and in solutions of single DNA Nucleoside Tri-Phosphates (dNTP), the molecular constituents that make up helical DNA. The spontaneous phase transition to columnar liquid crystals by the dNTPs occurs without the necessity of the sugar-phosphate backbone of helical DNA, and exhibits key structural elements of biologic nucleic acids including long-range columnar stacking of base-pairs and Watson-Crick selectivity. This spontaneous increase in structural complexity is useful when discussing liquid crystal formation as relevant to the increasingly complexity of prebiotic life.

Ribonucleic acid (RNA ...


Effect Of Variation In An Essential Folding Element On The Cobalamin Riboswitch, Marcus Urquijo Jan 2018

Effect Of Variation In An Essential Folding Element On The Cobalamin Riboswitch, Marcus Urquijo

Undergraduate Honors Theses

Riboswitches are RNA-based genetic regulatory elements that control gene expression without the need for protein cofactors. These RNA motifs are found within the 5’ untranslated regions of mRNA and promote genetic regulation by altering the structure of RNA through binding small molecule effector ligands that cause conformational changes that repress or activate translation/transcription. The env8 cobalamin riboswitch binds cyanocobalamin (CNCbl) to repress gene expression of the downstream mRNA. It accomplishes this through an interplay of two separate domains; an aptamer domain which binds the effector ligand and a regulatory domain which contains the genetic switch. Within the aptamer domain ...


Computational Modeling Of Mitosis In Fission Yeast, Christopher Edelmaier Jan 2018

Computational Modeling Of Mitosis In Fission Yeast, Christopher Edelmaier

Physics Graduate Theses & Dissertations

Mitosis ensures the proper segregation of chromosomes into daughter cells, which is accomplished by the mitotic spindle. During fission yeast mitosis, chromosomes establish bi-orientation as the bipolar spindle assembles, meaning that sister kinetochores become attached to microtubules whose growth was initiated by the two sister poles. This process includes mechanisms that correct erroneous attachments made by the kinetochores during the attachment process. This thesis presents a 3D physical model of spindle assembly in a Brownian dynamics-kinetic Monte Carlo simulation framework and a realistic description of the physics of microtubule, kinetochore, and chromosome dynamics, in order to interrogate the dynamics and ...


Dynamics Of Crowded And Active Biological Systems, Michael W. Stefferson Jan 2018

Dynamics Of Crowded And Active Biological Systems, Michael W. Stefferson

Physics Graduate Theses & Dissertations

Interactions between particles and their environment can alter the dynamics of biological systems. In crowded media like the cell, interactions with obstacles can introduce anomalous subdiffusion. Active matter systems, e.g., bacterial swarms, are nonequilibrium fluids where interparticle interactions and activity cause collective motion and dynamical phases. In this thesis, I discuss my advances in the fields of crowded media and active matter. For crowded media, I studied the effects of soft obstacles and bound mobility on tracer diffusion using a lattice Monte Carlo model. I characterized how bound motion can minimize the effects of hindered anomalous diffusion and obstacle ...


Liquid Crystals Formed By Short Dna Oligomers And The Origin Of Life, Gregory Patrick Smith Jan 2018

Liquid Crystals Formed By Short Dna Oligomers And The Origin Of Life, Gregory Patrick Smith

Physics Graduate Theses & Dissertations

When dissolved in water, base paired DNA oligomers form double helices with sufficient structural rigidity that, if they are at high enough concentration, can undergo a phase transition into chiral nematic or hexagonal columnar liquid crystalline (LC) order. Within these LC phases, constrained orientation allows these rods to stack more efficiently by hydrophobic forces than they would otherwise, building them into long double helical aggregates that can be chemically glued together (ligated) to further increase their lengths. Even in absence of chemical ligation, this stacking effect is strong enough that short DNA oligomers, which are otherwise too short to form ...


Development And Characterization Of Improved Red Fluorescent Protein Variants, Premashis Manna Jan 2018

Development And Characterization Of Improved Red Fluorescent Protein Variants, Premashis Manna

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

Aequorea victoria-based green fluorescent proteins and their blue, cyan and red counterparts offer unprecedented advantage as biological markers owing to their genetic encodability and straightforward expression in different organisms. Fluorescent proteins are characterized with complex photo-kinetics due to the presence of light-induced non-fluorescent or dark states which are responsible for their fluorescence intermittency or 'blinking'. We developed time- and frequency-domain techniques for probing the kinetics involving dark state conversion (DSC) and ground state recovery (GSR) in red fluorescent proteins (RFPs). Ensemble-level DSC and GSR kinetics in FPs were presented in the context of their single molecule fluorescence behaviors. Although ...


High Precision Afm-Based Smfs Of Mechanically Labile Type Iii Secretion System Effectors, Marc-Andre Leblanc Jan 2018

High Precision Afm-Based Smfs Of Mechanically Labile Type Iii Secretion System Effectors, Marc-Andre Leblanc

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

Pathogenic bacteria have developed a wide range of tools for circumventing or overcoming the host’s defenses. Over time, these tools have become increasingly complex, allowing bacteria to live and thrive within a wide variety of host environments. One such tool is the Type III Secretion System (T3SS), a needle-like complex that allows bacteria to directly inject proteins, known as effectors, from their cytoplasm into host cells. Once inside host cells, effector proteins have a wide range of effects, from shutting down the host immune response to rearranging the host cytoskeleton to accommodate invading bacteria.

Because the T3SS needle presents ...


Design And Synthesis Of Potential Tlr7 And Tlr8 Inhibitors, Patrick Nordeen Jan 2018

Design And Synthesis Of Potential Tlr7 And Tlr8 Inhibitors, Patrick Nordeen

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

Toll-like receptors (TLRs) detect invading viral and bacterial pathogens and play a critical role in the initiation and regulation of the innate immune system. Over-active TLR signaling has been indicated in the disease pathology of numerous crippling inflammatory autoimmune disorders and inhibition of these receptors is of considerable interest for therapeutic intervention. TLR7 and TLR8 are the two TLRs that share the most similarity in both sequence and structure. Despite their similarity, selective inhibition represents a promising therapy for diseases such as systemic lupus erythematosus (lupus) and rheumatoid arthritis (RA). The goal of this master’s thesis is to identify ...