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

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 ...


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 ...


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 ...


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 ...


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 ...


Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson Jan 2017

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 ...


Specificity Of Molecular Responses To Erk1/2 And Mkk1/2 Inhibitors In Melanoma Cells, Joel Michael Basken Jan 2017

Specificity Of Molecular Responses To Erk1/2 And Mkk1/2 Inhibitors In Melanoma Cells, Joel Michael Basken

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Skin cancer is the most commonly diagnosed cancer in the U.S. and 75% of skin cancer related deaths are due to malignant melanoma, a cancer originating in melanin producing melanocytes. The RAF/MKK/ERK signaling cascade is constitutively activated in over 90% of melanomas and 52% of tumors contain BRAF V600E/K oncogenic driver mutations. Although small molecule inhibitors specifically targeting mutant BRAF V600E/K and the downstream kinases MKK1/2 have been successful in clinical settings, resistance invariably develops. In preclinical studies, inhibitors of ERK1/2 can overcome resistance to BRAF V600E/K and MKK1/2 inhibitors, making ...


Pathways Of Adaptation: A Large-Scale Expression And Genotypic Analysis Of The Influence Of Polyploidy On The Evolution Of Yeast Grown In A Sub-Optimal Carbon Source, Amber Lynne Scott Jan 2017

Pathways Of Adaptation: A Large-Scale Expression And Genotypic Analysis Of The Influence Of Polyploidy On The Evolution Of Yeast Grown In A Sub-Optimal Carbon Source, Amber Lynne Scott

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Polyploidy, or having more than 2 full sets of chromosomes, has occurred in the evolution of many fungi, plant, and animal species and is thought to contribute to speciation. Despite the important role of polyploidy in evolution, little is known about how polyploidy contributes to adaptation and speciation. We previously showed that tetraploid yeast adapted significantly faster to growth under carbon stress compared to the haploid and diploid yeast, yet it was not clear what mechanisms drove the increase in the rate of evolution in the tetraploid strains. To answer this, I assessed the different pathways of adaption that the ...


Characterizing The Rna Binding Properties Of The Intrinsically Disordered Fus Protein And Rgg/Rg Domains, Bagdeser Akdogan Ozdilek Jan 2017

Characterizing The Rna Binding Properties Of The Intrinsically Disordered Fus Protein And Rgg/Rg Domains, Bagdeser Akdogan Ozdilek

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Recent developments in the comprehensive identification of the RNA-binding protein (RBP) repertoire has accelerated discovery of new RBPs. According to these studies, 20% of both known and novel RNA-binding proteins are highly disordered. Moreover, analysis of the human mRNA interactome revealed most disease related mutations are found within intrinsically disordered RNA-binding domains (RBDs). For most of these proteins, their RNA-binding properties are poorly characterized. Thus, deciphering intrinsically disordered RBD-RNA interactions on a molecular scale is essential to understanding their impact upon human physiology and diseases.

RGG/RG (arginine/glycine) domains are the second most common RNA binding domain in the ...


Biological Sex Differences In The Gene Expression And Contractile Function Of Cardiac Myocytes, Christa Lynn Trexler Jan 2017

Biological Sex Differences In The Gene Expression And Contractile Function Of Cardiac Myocytes, Christa Lynn Trexler

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Significant sexual dimorphisms have been demonstrated in the development, presentation and outcome of cardiovascular disease (CVD) in humans as well as in animal models. Biological sex is an important modifier of the development of CVD with younger women generally being protected, but this cardioprotection is lost later in life, suggesting a role for estrogen. Additionally, even though CVD is the number one killer of women in the U.S., women have traditionally been omitted from clinical trials and female animals have commonly been excluded from basic research studies. This research bias has led to the development of cardiovascular therapeutics that ...


Analysis Of Two Centrin-Binding Proteins, Poc5 And Sfr1, In Tetrahymena Thermophila Basal Bodies, Westley Heydeck Jan 2016

Analysis Of Two Centrin-Binding Proteins, Poc5 And Sfr1, In Tetrahymena Thermophila Basal Bodies, Westley Heydeck

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Basal bodies are microtubule-based structures which template, anchor, and orient cilia at the cell surface. Although basal bodies contribute to vital cell functions, the molecular contributors of their assembly and maintenance are poorly understood. Previous studies in Tetrahymena thermophila revealed important roles for centrins in basal body assembly, separation of new basal bodies, and stability. Here, I characterized the basal body function of two centrin-binding proteins, Sfr1 and Poc5, in Tetrahymena. Sfr1 is the only centrin-binding protein in Tetrahymena that localizes to all cortical row and oral apparatus basal bodies. Poc5, on the other hand, transiently localizes to basal bodies ...


Polyomavirus Interactions With Host Cell Surface Receptors Mediate Important Steps In Virus Infection: From Signaling To Pathogenesis, Samantha D. O'Hara Jan 2016

Polyomavirus Interactions With Host Cell Surface Receptors Mediate Important Steps In Virus Infection: From Signaling To Pathogenesis, Samantha D. O'Hara

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Virus binding to the cell surface triggers an array of host responses important for infection. Gangliosides are the cell surface receptors for Polyomavirus (PyV) infection. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1 and alterations in ganglioside binding cause dramatic changes in virus tropism and pathogenesis. Knockout mice lacking complex gangliosides are completely resistant to Mouse Polyomavirus (MuPyV) infection. Fibroblasts (MEFs) from these mice are likewise resistant to infection, and supplementation with specific gangliosides: GD1a, GT1b, and GT1a rescues infection. MuPyV also binds a protein receptor α4-integrin and loss of ...


Regulation Of Gene Expression By The Mediator Kinase Cdk19, Katherine Audrey Audetat Jan 2016

Regulation Of Gene Expression By The Mediator Kinase Cdk19, Katherine Audrey Audetat

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Mediator complex is a required co-activator of RNA Polymerase II (Pol II), the enzyme responsible for the transcription of all protein coding genes in eukaryotes. Mediator facilitates transcription factor-dependent gene expression by directly interacting with gene specific transcription factors and Pol II and the general transcription machinery. Mediator consists of up to 29 subunits; a four-subunit “CDK module” reversibly associates with Core-Mediator and alters its structure and activity. Most of the work on the CDK module has been done in yeast, and has focused on the CDK module subunits CDK8, MED12, and MED13. These three subunits have paralog proteins ...


Investigating The Molecular Mechanisms And Functions Of The Musashi-2 Rna-Binding Protein, Christopher Bennett Jan 2016

Investigating The Molecular Mechanisms And Functions Of The Musashi-2 Rna-Binding Protein, Christopher Bennett

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Musashi (Msi) family of RNA-binding proteins is post-transcriptional regulators of gene expression. They were discovered in 1994 as being required for Drosophila sensory organ development. Since then, Msi proteins have been found to enhance cell proliferation and maintain stem cell identities in a multitude of mammalian tissues. In addition, overexpression of Msi proteins is often observed in many types of human cancers, most prominently the widely expressed Msi family member, Musashi-2 (Msi2). Msi2 plays oncogenic roles in hematopoietic, neural, and gastrointestinal tissues. However, Msi2 has received little attention in other tissues in which it is expressed, such as in ...


Activation And Utilization Of Dna Damage Signaling By Murine Polyomavirus, Katie Heiser Jan 2016

Activation And Utilization Of Dna Damage Signaling By Murine Polyomavirus, Katie Heiser

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which may detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. I investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, ATM, RPA, MRN, and DNAPK. I found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK ...


Sexually Dimorphic Cardiac Adaptation Is Mediated By Cre Expression, Independent Of Estrogen-Receptor-Α Expression, Emily K. Pugach Jan 2015

Sexually Dimorphic Cardiac Adaptation Is Mediated By Cre Expression, Independent Of Estrogen-Receptor-Α Expression, Emily K. Pugach

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The mammalian heart is a remarkably adaptable organ. In particular, the contractile cells of the heart, the cardiac myocytes can respond to dramatic changes in metabolic and functional demand. Both clinical data and murine genetic studies suggest fundamental differences in male and female cardiac biology, including at the cellular level of the myocyte. In this thesis, I address the clinical question of why cardiovascular disease differs in males and females at the cardiac myocyte level. Specifically, I elucidate the importance and mechanism of estrogen signaling in male and female cardiac myocytes. Upon identifying Estrogen Receptor-α (ERα) as the predominant estrogen ...


Regulatory Organization And Transcriptional Response Of Sphingobium Chlorophenolicum To The Anthropogenic Pesticide Petachlorophenol, Joe Franklin Rokicki Jan 2015

Regulatory Organization And Transcriptional Response Of Sphingobium Chlorophenolicum To The Anthropogenic Pesticide Petachlorophenol, Joe Franklin Rokicki

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The sudden and widespread introduction of the pesticide pentachlorophenol (PCP) into the environment from 1930 to 1980 created a new global selection pressure on microbes. The subsequent isolation of a pentachlorophenol degrading bacterium, Sphingobium chlorophenolicum, provided a unique opportunity to study an early evolutionary response to the new selective pressure.

The minimal enzymatic pathway required to degrade PCP was laboriously determined before high throughput sequencing was possible. Many of the proteins discovered were identified by following their activities through increasingly stringent fractionations, sequencing the N terminus of the protein, designing degenerate primers, and ultimately cloning the gene from the genome ...


A Computational And Evolutionary Approach To Understanding Cryptic Unstable Transcripts In Yeast, Jessica Marie Vera Jan 2015

A Computational And Evolutionary Approach To Understanding Cryptic Unstable Transcripts In Yeast, Jessica Marie Vera

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Cryptic unstable transcripts (CUTs) are a largely unexplored class of nuclear exosome degraded, non-coding RNAs in budding yeast. It is highly debated whether CUT transcription has a functional role in the cell or whether CUTs represent noise in the yeast transcriptome. I sought to ascertain the extent of conserved CUT expression across a variety of Saccharomyces yeast strains to further understand and characterize the nature of CUT expression. To this end I designed a Hidden Markov Model (HMM) to analyze strand-specific RNA sequencing data from nuclear exosome rrp6Δ mutants to identify and compare CUTs in four different yeast strains ...


Mirnas Collaborate With A Conserved Rna Binding Protein To Ensure Development And Stress Response In C. Elegans, Rebecca A. Zabinsky Jan 2015

Mirnas Collaborate With A Conserved Rna Binding Protein To Ensure Development And Stress Response In C. Elegans, Rebecca A. Zabinsky

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

miRNAs play critical roles in development and other cellular processes in C. elegans even though most individual miRNAs are not essential for development or viability (Miska et al., 2007). Extensive studies in the field have suggested that most miRNA functions are executed through complex miRNA-target interaction networks. Furthermore, such networks may also function semi-redundantly with other regulatory systems to shape gene expression dynamics for proper physiological functions. Hypothesizing that miRNAs function in stress conditions, I collaborated with a postdoctoral fellow to investigate the role of a specific miRNA miR-71 in starvation induced L1 diapause. Hypothesizing that miRNAs collaborate with other ...


A New Role For The Endoplasmic Reticulum At Endosome Contact Sites, Ashley Ann Rowland Jan 2015

A New Role For The Endoplasmic Reticulum At Endosome Contact Sites, Ashley Ann Rowland

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Endoplasmic Reticulum (ER) forms a dynamic network that spans throughout the cell. In addition to the well characterized roles in lipid synthesis, protein folding, and calcium handling, the ER coordinates important functions at stable membrane contact sites formed with other organelles. Recent work from the lab demonstrated that ER tubules circumscribe mitochondrial constrictions and define the position of mitochondrial fission. We predicted that mechanisms of membrane fission are conserved between various organelles. Here we hypothesized and tested whether ER contacts define the timing and the position of endosome fission. Endocytic cargo and Rab GTPases are segregated to distinct domains ...


Identification Of Novel Microrna Targets And Tumor Suppressive Functions Of Mir-203 In Murine Skin, Kent Augustus Riemondy Jr. Jan 2015

Identification Of Novel Microrna Targets And Tumor Suppressive Functions Of Mir-203 In Murine Skin, Kent Augustus Riemondy Jr.

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

miRNAs are small non-coding RNAs, approximately 22 nucleotide in length, that mediate post-transcriptional repression of target mRNAs. Since their discovery in mammals in the early 2000s, miRNAs have been intensely studied and determined to be an important mechanism to regulate gene expression in diverse biological processes. In human cancers, miRNAs are known to act as tumor suppressors or oncogenes and are being actively explored as a possible mechanism for therapeutic intervention. In the mouse, multistage skin carcinogenesis is a well-established model for studying tumor development however the functions of miRNAs in this model are poorly understood.

The Ras oncogene was ...


Responses To Ionizing Radiation And Translation Inhibition In Drosophila Melanogaster And Human Cancer Cells, Stefanie Michaela Stickel Jan 2014

Responses To Ionizing Radiation And Translation Inhibition In Drosophila Melanogaster And Human Cancer Cells, Stefanie Michaela Stickel

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

A common regimen for the treatment of solid tumors includes ionizing radiation (IR), chemotherapies, and targeted agents, such as kinase inhibitors. Cancer therapies have been traditionally tailored to the tissue origin of the tumor, rather than the mutation type; however, this concept has been changing with evidence that agents targeted to specific mutations are effective in many cancer types. The latter theory assumes that inhibition of the oncogenic mutation trumps differences between tissues, a concept that has never been proven in a whole organism. My results in the first half of this thesis show for the first time that isogenic ...


A Novel Selection Technology For The Discovery Of High-Affinity Human Proteins, David Busha Jan 2014

A Novel Selection Technology For The Discovery Of High-Affinity Human Proteins, David Busha

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Proteins that bind with high-affinity to cellular targets can be useful therapeutic treatments. High-throughput affinity screening of large protein libraries is often more successful at discovering novel high-affinity proteins than rational-design approaches. Display techniques such and phage and yeast display are commonly used in this screening process. However, bacteria and yeast cells can misfold or otherwise inappropriately express mammalian and human proteins due to differences in codon usage, protein folding machinery and post-translational modifications. Therefore, a display system that is entirely based in human cells could aid in the discovery of novel, high-affinity proteins. No such system has been described ...


Examining Post-Transcriptional Regulation Of Skeletal Muscle Satellite Cell Homeostasis, Activation And Fate Determination, Crystal Dawn Pulliam Jan 2014

Examining Post-Transcriptional Regulation Of Skeletal Muscle Satellite Cell Homeostasis, Activation And Fate Determination, Crystal Dawn Pulliam

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Skeletal muscle is essential for respiration, mobility, reproduction and metabolism. Deficits in muscle function due to disease, injury or age reduce both quality of life and lifespan. Muscles are long-lived tissues that require maintenance to retain functional integrity throughout the life of an organism. Satellite cells are the adult stem cells responsible for muscle repair and maintenance. Upon myotrauma, satellite cells re-enter the cell cycle, proliferate, and terminally differentiate to repair the muscle. In uninjured tissue, satellite cells are quiescent and infrequently proceed through myogenesis for muscle maintenance. The molecular mechanisms that regulate satellite cell quiescence and activation are poorly ...