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Genetics

2017

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Articles 1 - 30 of 41

Full-Text Articles in Molecular Biology

Identification Of Factors Involved In 18s Nonfunctional Ribosomal Rna Decay And A Method For Detecting 8-Oxoguanosine By Rna-Seq, Kelly A. Limoncelli Dec 2017

Identification Of Factors Involved In 18s Nonfunctional Ribosomal Rna Decay And A Method For Detecting 8-Oxoguanosine By Rna-Seq, Kelly A. Limoncelli

GSBS Dissertations and Theses

The translation of mRNA into functional proteins is essential for all life. In eukaryotes, aberrant RNAs containing sequence features that stall or severely slow down ribosomes are subject to translation-dependent quality control. Targets include mRNAs encoding a strong secondary structure (No-Go Decay; NGD) or stretches of positively-charged amino acids (Peptide-dependent Translation Arrest/Ribosome Quality Control; PDTA/RQC), mRNAs lacking an in-frame stop codon (Non-Stop Decay; NSD), or defective 18S rRNAs (18S Nonfunctional rRNA Decay; 18S NRD). Previous work from our lab showed that the S. cerevisiae NGD factors DOM34 and HBS1, and PDTA/RQC factor ASC1, all participate in the ...


Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone Dec 2017

Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone

Theses and Dissertations

Foodborne illnesses are a leading cause of infectious diseases in the world. Among enteric organisms Salmonella is a key pathogen. It’s high prevalence in poultry and other food-animal sources make it imperative to study. Salmonella has the ability to modify its genetic content with help of mobile genetic elements such as plasmids. Incompatibiltiy group 1 (IncI1) plasmids are commonly reported in Salmonella. This study evaluates role on IncI1 plasmids in antimicrobial resistance and virulence in Salmonella. Genetic determinants of resistance and virulence are noted among our IncI1-containing Salmonella isolates. These genetic elements are also transferable and reported to carry ...


High-Throughput Single-Molecule Telomere Characterization, Jennifer Mccaffrey, Eleanor Young, Katy Lassahn, Justin Sibert, Steven Pastor, Harold Riethman, Ming Xiao Nov 2017

High-Throughput Single-Molecule Telomere Characterization, Jennifer Mccaffrey, Eleanor Young, Katy Lassahn, Justin Sibert, Steven Pastor, Harold Riethman, Ming Xiao

Medical Diagnostics & Translational Sciences Faculty Publications

We have developed a novel method that enables global subtelomere and haplotype-resolved analysis of telomere lengths at the single-molecule level. An in vitro CRISPR/Cas9 RNA-directed nickase system directs the specific labeling of human (TTAGGG) n DNA tracts in genomes that have also been barcoded using a separate nickase enzyme that recognizes a 7bp motif genome-wide. High-throughput imaging and analysis of large DNA single molecules from genomes labeled in this fashion using a nanochannel array system permits mapping through subtelomere repeat element (SRE) regions to unique chromosomal DNA while simultaneously measuring the (TTAGGG) n tract length at the end of ...


Performing A Genetic Screen To Identify Factors That Promote Lncrna-Dependent Gene Repression, Chrishan Fernando, Cecilia Yiu, Sara Cloutier, Siwen Wang, Elizabeth Tran Aug 2017

Performing A Genetic Screen To Identify Factors That Promote Lncrna-Dependent Gene Repression, Chrishan Fernando, Cecilia Yiu, Sara Cloutier, Siwen Wang, Elizabeth Tran

The Summer Undergraduate Research Fellowship (SURF) Symposium

Long non-coding RNAs (lncRNAs) were once thought not to have useful functions in organisms but rather to be products of aberrant transcription. However, roles are being found for lncRNAs in beneficial processes such as controlling gene expression. In some of these cases, lncRNAs form R-loops in vivo. R-loops are nucleic acid structures consisting of hybridized strands of single-stranded DNA (ssDNA) and single-stranded RNA (ssRNA) as well as the displaced strand of ssDNA. Formation of these R-loops is important for gene regulation by the lncRNAs. However, factors that promote formation of lncRNA R-loops are not known. The gene PHO84 is being ...


New Insights Into The Role Of Antimicrobials Of Xenorhabdus In Interspecies Competition, Kristin Jean Ciezki Aug 2017

New Insights Into The Role Of Antimicrobials Of Xenorhabdus In Interspecies Competition, Kristin Jean Ciezki

Theses and Dissertations

Xenorhabdus spp. are symbionts of entomopathogenic nematodes and pathogens of susceptible insects. The nematodes penetrate the insect midgut to enter the hemocoel where Xenorhabdus bacteria are released, transitioning to their pathogenic stage. During nematode invasion microbes from the insect gut translocate into the hemocoel. In addition, different species of nematodes carrying specific strains of Xenorhabdus can invade a single insect. Xenorhabdus spp thereby engage in competition with both related strains and nonrelated gut microbes. In complex media Xenorhabdus spp produce diverse antimicrobial compounds whose functions in biological systems remain poorly understood. R-type bacteriocins are contractile phage-tail-like structures that are bactericidal ...


The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers Aug 2017

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and ...


Genome Wide Association And Next Generation Sequencing Approaches To Map Determinants Of Ascites In Broiler Chickens, Shatovisha Dey Aug 2017

Genome Wide Association And Next Generation Sequencing Approaches To Map Determinants Of Ascites In Broiler Chickens, Shatovisha Dey

Theses and Dissertations

These studies have investigated different candidate genomic regions for their contributions to ascites in broilers. Ascites syndrome is a manifestation of idiopathic pulmonary arteriole hypertension that concerns the poultry industry worldwide. Investigations have demonstrated the disease to be genetically regulated and to exhibit moderate to high heritabilities. Although previous studies have indicated a few chromosomes to be involved with ascites, no genes have been identified to date with direct links to the disease. This dissertation presents a collection of studies that determine the genomic and genetic interactions for regions on chromosome 2 and 9 for ascites phenotypes in broiler chickens ...


Comprehensive Assessments Of The Genetic Determinants In Salmonella Typhimurium For Fitness Under Host Stressors: Oxidative Stress And Iron Restriction, Sardar Abdullah Aug 2017

Comprehensive Assessments Of The Genetic Determinants In Salmonella Typhimurium For Fitness Under Host Stressors: Oxidative Stress And Iron Restriction, Sardar Abdullah

Theses and Dissertations

Salmonella is an intracellular pathogen that infects a wide range of hosts. The infected host utilizes reactive oxygen species (ROS) and iron-restriction to eliminate the pathogen. We used proteogenomics to determine the candidate genes and proteins that have a role in resistance of S. Typhimurium to H2O2. For Tn-seq, a highly saturated Tn5 library was grown in vitro under either 2.5 (H2O2L) or 3.5 mM H2O2 (H2O2H). We identified two sets of overlapping genes that are required for resistance of S. Typhimurium to H2O2L and H2O2H, and the results were validated via phenotypic evaluation of 50 selected mutants ...


Single-Molecule Studies Of Replication Kinetics In Response To Dna Damage, Divya Ramalingam Iyer May 2017

Single-Molecule Studies Of Replication Kinetics In Response To Dna Damage, Divya Ramalingam Iyer

GSBS Dissertations and Theses

In response to DNA damage during S phase, cells slow DNA replication. This slowing is orchestrated by the intra-S checkpoint and involves inhibition of origin firing and reduction of replication fork speed. Slowing of replication allows for tolerance of DNA damage and suppresses genomic instability. Although the mechanisms of origin inhibition by the intra-S checkpoint are understood, major questions remain about how the checkpoint regulates replication forks: Does the checkpoint regulate the rate of fork progression? Does the checkpoint affect all forks, or only those encountering damage? Does the checkpoint facilitate the replication of polymerase-blocking lesions? To address these questions ...


Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot May 2017

Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot

Electronic Thesis and Dissertation Repository

Despite the use of the host for dispersal by most parasite species, the extremely loose relationship typical between highly mobile hosts and generalist ectoparasites may lead to very different gene flow patterns between the two, leading in turn to different spatial genetic structure, and potentially different demographic history. I examined how similar gene flow patterns are between Cimex adjunctus, a generalist ectoparasite of bats present throughout North America, and two of its key bat hosts. I first analyzed the continent-scale genetic structure and demographic history of C. adjunctus and compared it to that of two of its hosts, the little ...


Three-Dimensional Folding Of Eukaryotic Genomes, Tsung-Han S. Hsieh May 2017

Three-Dimensional Folding Of Eukaryotic Genomes, Tsung-Han S. Hsieh

GSBS Dissertations and Theses

Chromatin packages eukaryotic genomes via a hierarchical series of folding steps, encrypting multiple layers of epigenetic information, which are capable of regulating nuclear transactions in response to complex signals in environment. Besides the 1-dimensinal chromatin landscape such as nucleosome positioning and histone modifications, little is known about the secondary chromatin structures and their functional consequences related to transcriptional regulation and DNA replication. The family of chromosomal conformation capture (3C) assays has revolutionized our understanding of large-scale chromosome folding with the ability to measure relative interaction probability between genomic loci in vivo. However, the suboptimal resolution of the typical 3C techniques ...


A New Era Of Genome Modification, Lizabeth R. Hampton Apr 2017

A New Era Of Genome Modification, Lizabeth R. Hampton

Honors Theses AY 16/17

Four decades ago, the advent of technology that could be applied to genetic engineering stimulated the hope that one day we would be able to ‘fix’ genetic disorders or inhibit cancer growth by replacing defective genes or introducing helpful genes into a person’s genome. That hope was followed by frustration with the limitations of the technology until the recent development of a new strategy used in the CRISPR/Cas9 system, which is considered one of the most important developments in the field of genome modification to date. CRISPR technology can be used both for genome modification and post-transcriptional editing ...


Genetic Variation In Concentration Of The 33-Mer Protein Subcomponent In Wheat, Robert L. Paris, Kaleb M. Pauley, Ryan K. Lokkesmoe, Sarah E. Lyon, James C. Dunlap, Julia M. Pierre, Timothy Vanwingerden, Finny J. Johns, Kyle J. Kilchrist, Tyler J. Reid, Caleb M. Winn Apr 2017

Genetic Variation In Concentration Of The 33-Mer Protein Subcomponent In Wheat, Robert L. Paris, Kaleb M. Pauley, Ryan K. Lokkesmoe, Sarah E. Lyon, James C. Dunlap, Julia M. Pierre, Timothy Vanwingerden, Finny J. Johns, Kyle J. Kilchrist, Tyler J. Reid, Caleb M. Winn

Robert L. Paris, Ph.D.

Celiac Disease is a hypersensitive response to gluten caused by HLA-DQ2 or HLA-DQ8 T-cell presentation, initiating destruction of intestinal epithelial cells. Currently, the only remedy for those suffering from celiac disease is elimination of all gluten from the diet. Studies indicate that an indigestible fragment of the gluten molecule, alpha-gliadin subcomponent 33-mer, rich in proline and glutamine, is responsible for the hypersensitivity response. Determination of 33-mer concentration in wheat lines could be beneficial to future development of wheat lines with reduced 33-mer concentration. Protein from wheat flour was extracted and subjected to ELISA techniques in order to quantify the concentration ...


Genetic Variation In Concentration Of The 33-Mer Protein Subcomponent In Wheat, Robert L. Paris, Kaleb M. Pauley, Ryan K. Lokkesmoe, Sarah E. Lyon, James C. Dunlap, Julia M. Pierre, Timothy Vanwingerden, Finny J. Johns, Kyle J. Kilchrist, Tyler J. Reid, Caleb M. Winn Apr 2017

Genetic Variation In Concentration Of The 33-Mer Protein Subcomponent In Wheat, Robert L. Paris, Kaleb M. Pauley, Ryan K. Lokkesmoe, Sarah E. Lyon, James C. Dunlap, Julia M. Pierre, Timothy Vanwingerden, Finny J. Johns, Kyle J. Kilchrist, Tyler J. Reid, Caleb M. Winn

Kaleb M. Pauley, Ph.D.

Celiac Disease is a hypersensitive response to gluten caused by HLA-DQ2 or HLA-DQ8 T-cell presentation, initiating destruction of intestinal epithelial cells. Currently, the only remedy for those suffering from celiac disease is elimination of all gluten from the diet. Studies indicate that an indigestible fragment of the gluten molecule, alpha-gliadin subcomponent 33-mer, rich in proline and glutamine, is responsible for the hypersensitivity response. Determination of 33-mer concentration in wheat lines could be beneficial to future development of wheat lines with reduced 33-mer concentration. Protein from wheat flour was extracted and subjected to ELISA techniques in order to quantify the concentration ...


Genetic Variation In Concentration Of The 33-Mer Protein Subcomponent In Wheat, Robert L. Paris, Kaleb M. Pauley, Ryan K. Lokkesmoe, Sarah E. Lyon, James C. Dunlap, Julia M. Pierre, Timothy Vanwingerden, Finny J. Johns, Kyle J. Kilchrist, Tyler J. Reid, Caleb M. Winn Apr 2017

Genetic Variation In Concentration Of The 33-Mer Protein Subcomponent In Wheat, Robert L. Paris, Kaleb M. Pauley, Ryan K. Lokkesmoe, Sarah E. Lyon, James C. Dunlap, Julia M. Pierre, Timothy Vanwingerden, Finny J. Johns, Kyle J. Kilchrist, Tyler J. Reid, Caleb M. Winn

The Research and Scholarship Symposium

Celiac Disease is a hypersensitive response to gluten caused by HLA-DQ2 or HLA-DQ8 T-cell presentation, initiating destruction of intestinal epithelial cells. Currently, the only remedy for those suffering from celiac disease is elimination of all gluten from the diet. Studies indicate that an indigestible fragment of the gluten molecule, alpha-gliadin subcomponent 33-mer, rich in proline and glutamine, is responsible for the hypersensitivity response. Determination of 33-mer concentration in wheat lines could be beneficial to future development of wheat lines with reduced 33-mer concentration. Protein from wheat flour was extracted and subjected to ELISA techniques in order to quantify the concentration ...


Molecular Regulation Of Stem Cell Behavior During Tissue Repair And Cancer Formation, Nestor J. Oviedo Mar 2017

Molecular Regulation Of Stem Cell Behavior During Tissue Repair And Cancer Formation, Nestor J. Oviedo

Science Seminar Series

Oviedo will be presenting his work on identifying the mechanisms of adult stem cell fate determination based on their topographical location in the adult body. Understanding stem cell fate determination is crucial because tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. Despite its critical implications for stem cell biology, carcinogenesis and regenerative medicine, this physiological phenomenon has remained overlooked. Recent findings from his group provide intriguing evidence implying DNA repair mechanisms and cellular signaling through post-translational modifications regulate stem cell fate decision depending on their topographical location in the adult body. We ...


Quantitative Limits On Small Molecule Transport Via The Electropermeome - Measuring And Modeling Single Nanosecond Perturbations, Esin B. Sözer, Zachary A. Levine, P. Thomas Vernier Mar 2017

Quantitative Limits On Small Molecule Transport Via The Electropermeome - Measuring And Modeling Single Nanosecond Perturbations, Esin B. Sözer, Zachary A. Levine, P. Thomas Vernier

Bioelectrics Publications

The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical parameters in existing models must be replaced with physics- and biology-based terms anchored in experimental observations. We report here absolute values for the uptake of YO-PRO-1, a small-molecule fluorescent indicator of membrane integrity, into cells after a single electric pulse lasting only 6 ns. We correlate these measured values, based on fluorescence microphotometry of hundreds of individual cells, with a diffusion-based geometric analysis of pore-mediated ...


The Intra-S Checkpoint Responses To Dna Damage, Divya Ramalingam Iyer, Nicholas R. Rhind Feb 2017

The Intra-S Checkpoint Responses To Dna Damage, Divya Ramalingam Iyer, Nicholas R. Rhind

Open Access Articles

Faithful duplication of the genome is a challenge because DNA is susceptible to damage by a number of intrinsic and extrinsic genotoxins, such as free radicals and UV light. Cells activate the intra-S checkpoint in response to damage during S phase to protect genomic integrity and ensure replication fidelity. The checkpoint prevents genomic instability mainly by regulating origin firing, fork progression, and transcription of G1/S genes in response to DNA damage. Several studies hint that regulation of forks is perhaps the most critical function of the intra-S checkpoint. However, the exact role of the checkpoint at replication forks has ...


A Microrna Family Exerts Maternal Control On Sex Determination In C. Elegans, Katherine Mcjunkin, Victor R. Ambros Feb 2017

A Microrna Family Exerts Maternal Control On Sex Determination In C. Elegans, Katherine Mcjunkin, Victor R. Ambros

Program in Molecular Medicine Publications and Presentations

Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally contributed microRNAs may therefore play important roles in early development. We elucidated a major biological role of the nematode mir-35 family of maternally contributed essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream of and downstream from her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. Both of the predicted target genes that act downstream from the mir-35 family in this process, suppressor-26 (sup-26) and NHL (NCL-1, HT2A, and LIN-41 repeat) domain-containing-2 (nhl-2), encode RNA-binding ...


Investigating The Essential Roles Of Dprl-1 In Drosophila Melanogaster, Alex Lee Jan 2017

Investigating The Essential Roles Of Dprl-1 In Drosophila Melanogaster, Alex Lee

Summer Research

Phosphatase of Regenerating Liver (PRL) proteins regulate a number of important cellular processes, including cell growth and division. Humans have three PRL proteins: PRL-1, PRL-2, and PRL-3. An accumulation of evidence has shown that elevated levels of PRLs are strongly correlated with uncontrollable growth and metastasis of tumors. However, contradictory findings have arisen indicating that PRLs instead function to halt cell division thereby preventing uncontrollable tumor growth. In light of these results, the underlying mechanisms regarding how PRLs function within cellular processes remains unclear. To investigate the functions of PRLs, we will create transgenic fruit flies (Drosophila melanogaster) with knockout ...


The Effect Of Acetylation Of Cytochrome C On Its Functions In Prostate Cancer, Viktoriia Bazylianska Jan 2017

The Effect Of Acetylation Of Cytochrome C On Its Functions In Prostate Cancer, Viktoriia Bazylianska

Wayne State University Theses

Prostate cancer is the second leading cause of cancer death among men in America. The progression of cancer goes along with the Warburg effect, a metabolic switch from depending primarily on mitochondrial respiration to glycolysis. In addition, cancer cells manage to evade apoptosis. Cell signaling, via posttranslational modifications (PTMs), is one of the most important means of regulation, and most commonly dysregulated in cancer. In prostate cancer, androgen signaling plays a crucial role in driving cell proliferation.

Mammalian Cytochrome c (Cytc) is a multifunctional protein involved in cellular life and death decision. It is an essential component of the electron ...


Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki Jan 2017

Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki

Wayne State University Dissertations

The work of this project was to develop, test and characterize a potential novel mouse model of the neurodegenerative disease Multiple Sclerosis (MS). Historically, MS has been identified as a primary autoimmune disease of the central nervous system (CNS). However, treatments based on this view have met with limited success, and in most cases, fail to prevent progression of MS from mild to moderate and severe forms. Original observations regarding axonal and neuronal pathology in the white and gray matter of the CNS were rediscovered in the 1990s. These observations indicated that even in the absence of the immune system ...


Sh3 And Multiple Ankyrin Repeat Domain 3 (Shank3) Affects The Expression Of Hyperpolarization-Activated Cyclic Nucleotide-Gated (Hcn) Channels In Mouse Models Of Autism, Nikhil N. Shah Jan 2017

Sh3 And Multiple Ankyrin Repeat Domain 3 (Shank3) Affects The Expression Of Hyperpolarization-Activated Cyclic Nucleotide-Gated (Hcn) Channels In Mouse Models Of Autism, Nikhil N. Shah

Theses and Dissertations

SH3 and multiple ankyrin repeat domains 3 (SHANK3) is a multidomain scaffold protein that is highly augmented in the postsynaptic density (PSD) of excitatory glutamatergic synapses within the central and peripheral nervous systems. SHANK3 links neurotransmitter receptors, ion channels, and other critical membrane proteins to intracellular cytoskeleton and signal transduction pathways. Mutations in SHANK3 are linked with a number neuropsychiatric disorders including autism spectrum disorders (ASDs). Intellectual disability, impaired memory and learning, and epilepsy are some of the deficits commonly associated with ASDs that result from mutations in SHANK3. Interestingly, these symptoms show some clinical overlap with presentations of human ...


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 ...


Investigations Into Nutritional Quality, Commercial Productivity, And Genetic Purity Of Maize Grain For Organic Production Systems, Ryan Huffman Jan 2017

Investigations Into Nutritional Quality, Commercial Productivity, And Genetic Purity Of Maize Grain For Organic Production Systems, Ryan Huffman

Graduate Theses and Dissertations

Consumer demand for organic maize grain has steadily increased in the past decade which has resulted in an increased interest for this market class by plant breeders and geneticist. Each chapter in this dissertation investigates areas of concern to the organic community and possible solutions for improvement. Chapter 2 seeks to understand which combinations of genetic mechanisms are capable of a further increase in the methionine concentration of maize grain over individual mechanisms. Based on the genetic mechanisms evaluated, it was concluded that crosses combining dzr1 and recurrent selection in hybrid combination can elevate methionine concentration and overall grain nutritional ...


Insights Into Retinal Cell Fate Determination In Vertebrates Using Transcriptomic Profiling And Genome Editing, Rebecca Chowdhury Jan 2017

Insights Into Retinal Cell Fate Determination In Vertebrates Using Transcriptomic Profiling And Genome Editing, Rebecca Chowdhury

Graduate Theses and Dissertations

Deciphering the mechanisms of development of retinal neurons is not only of immense interest to developmental biologists, but is also vital for regenerative therapeutic applications. To attain this goal, it is critical to understand how specific intrinsic factors control cell fate decisions and neuronal maturation processes. In the retina, Atoh7 is a highly conserved transcription factor that is essential for retinal ganglion cell development in the developing mouse and zebrafish. Atoh7 labels a subset of cells in the developing retina that are progressing from a progenitor to a differentiated state. To capture cells during the window when the cell fate ...


The Key Question In Symbiotic Nitrogen Fixation: How Does Host Maintain A Bacterial Symbiont?, Onur Oztas Jan 2017

The Key Question In Symbiotic Nitrogen Fixation: How Does Host Maintain A Bacterial Symbiont?, Onur Oztas

Doctoral Dissertations

The fact that plants cannot use nitrogen in the gaseous form makes them dependent on the levels of usable nitrogen forms in the soil. Legumes overcome nitrogen limitation by entering a symbiotic association with rhizobia, soil bacteria that convert atmospheric nitrogen into usable ammonia. In root nodules, bacteria are internalized by host plant cells inside an intracellular compartment called the symbiosome where they morphologically differentiate into nitrogen-fixing forms by symbiosome-secreted host proteins.

In this project, I explained the host proteins required to maintain bacterial symbionts and described their delivery to the symbiosome. I showed that the SYNTAXIN 132 (SYP132) gene ...


Dissecting The Functions Of Atr In Replication Fork Stability, Theonie Anastassiadis Jan 2017

Dissecting The Functions Of Atr In Replication Fork Stability, Theonie Anastassiadis

Publicly Accessible Penn Dissertations

Genome maintenance is required for cellular viability, and failure to preserve genomic integrity is associated with an increased risk of diseases, such as cancer. To ensure genomic stability, cells have checkpoints that control cell cycle progression in the event of DNA damage or incomplete DNA replication. The DNA replication checkpoint is regulated by the ATR-CHK1 pathway that stabilizes stalled replication forks and prevents their collapse into DNA double-strand breaks (DSBs). Two distinct models have been proposed to explain how ATR stabilizes stalled forks: 1) through local modulation of fork remodelers, such as SMARCAL1 inhibition, and 2) through inhibition of CDK-dependent ...


Novel Cell Surface Anchoring Mechanism Of Prokaryotic Secreted Protein, Mohd Farid Abdul Halim Jan 2017

Novel Cell Surface Anchoring Mechanism Of Prokaryotic Secreted Protein, Mohd Farid Abdul Halim

Publicly Accessible Penn Dissertations

The microbial cell surface is decorated with a variety of protein structures that play important roles in key cellular processes such as providing cell stability, facilitating interactions between cells, and interacting with the environment. One important feature of the biosynthesis of these structures is the proper anchoring of proteins to the cell surface. In silico work recently predicted a novel protein anchoring mechanism for a subset of surface proteins that contain a conserved C-terminal tripartite architecture, which consists of a conserved motif, followed by a hydrophobic (H) domain, and positively charged amino acids. Using the well-studied model archaeon Haloferax volcanii ...


The Human Heterochromatin Landscape: Genomic Subtypes, Bound Proteins, And Contributions To Cell Identity, Justin S. Becker Jan 2017

The Human Heterochromatin Landscape: Genomic Subtypes, Bound Proteins, And Contributions To Cell Identity, Justin S. Becker

Publicly Accessible Penn Dissertations

Large portions of mammalian genomes are packaged into structurally compact heterochromatin, which protects genome integrity and suppresses transcription of lineage-inappropriate genes. Characterization of heterochromatic regions has relied on genomic mapping of associated histone modifications, such as H3K9me3 and H3K27me3, and purification of proteins interacting with these modifications. Heterochromatic regions marked by H3K9me3 have been shown to impede gene activation during reprogramming to pluripotency, and I find that H3K9me3 domains can similarly impede conversion of fibroblasts to hepatocytes. However, both H3K9me3 and H3K27me3 can be found in transcriptionally active chromatin, limiting the accuracy of histone marks alone for identifying heterochromatin domains ...