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Genetics

2016

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Articles 1 - 30 of 42

Full-Text Articles in Molecular Biology

Dna Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent Of Error-Prone Synthesis, And The Role Of Dntp Pools, Olga V. Kochenova Dec 2016

Dna Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent Of Error-Prone Synthesis, And The Role Of Dntp Pools, Olga V. Kochenova

Theses & Dissertations

Despite multiple DNA repair pathways, DNA lesions can escape repair and compromise normal chromosomal replication, leading to genome instability. Cells utilize specialized low-fidelity Translesion Synthesis (TLS) DNA polymerases to bypass lesions and rescue arrested replication forks. TLS is a highly conserved two-step process that involves insertion of a nucleotide opposite a lesion and extension of the resulting aberrant primer terminus. The first step can be performed by both replicative and TLS DNA polymerases and, because of non-instructive DNA lesions, often results in a nucleotide misincorporation. The second step is almost exclusively catalyzed by DNA polymerase ζ ...


A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout Oct 2016

A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout

Open Access Articles

Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90 ...


Ataluren Stimulates Ribosomal Selection Of Near-Cognate Trnas To Promote Nonsense Suppression, Bijoyita Roy, Westley J. Friesen, Yuki Tomizawa, John D. Leszyk, Jin Zhuo, Briana Johnson, Jumana Dakka, Christopher R. Trotta, Xiaojiao Xue, Venkateshwar Mutyam, Kim M. Keeling, James A. Mobley, Steven M. Rowe, David M. Bedwell, Ellen M. Welch, Allan Jacobson Oct 2016

Ataluren Stimulates Ribosomal Selection Of Near-Cognate Trnas To Promote Nonsense Suppression, Bijoyita Roy, Westley J. Friesen, Yuki Tomizawa, John D. Leszyk, Jin Zhuo, Briana Johnson, Jumana Dakka, Christopher R. Trotta, Xiaojiao Xue, Venkateshwar Mutyam, Kim M. Keeling, James A. Mobley, Steven M. Rowe, David M. Bedwell, Ellen M. Welch, Allan Jacobson

Microbiology and Physiological Systems Publications and Presentations

A premature termination codon (PTC) in the ORF of an mRNA generally leads to production of a truncated polypeptide, accelerated degradation of the mRNA, and depression of overall mRNA expression. Accordingly, nonsense mutations cause some of the most severe forms of inherited disorders. The small-molecule drug ataluren promotes therapeutic nonsense suppression and has been thought to mediate the insertion of near-cognate tRNAs at PTCs. However, direct evidence for this activity has been lacking. Here, we expressed multiple nonsense mutation reporters in human cells and yeast and identified the amino acids inserted when a PTC occupies the ribosomal A site in ...


Study Of The Structure-Related Functions Of Eukaryotic Primase-Pol Alpha Complex During Replication, Yinbo Zhang Aug 2016

Study Of The Structure-Related Functions Of Eukaryotic Primase-Pol Alpha Complex During Replication, Yinbo Zhang

Theses & Dissertations

During eukaryotic replication primase•polymerase α (prim•polα) complex synthesizes de novo chimeric primers composed of about 10 nt RNA and 20 nt DNA, which are subsequently extended by main replicative DNA polymerases (pol), polε and polδ, on leading and lagging strands, respectively. It is estimated that prim•polα initiates more than 10 millions of lagging strand Okazaki fragments in human genome in each replication cycle. A concerted action of the two active sites, RNA pol and DNA pol, is required to ensure the efficient priming. A remarkable feature of the prim•polα complex is the “programmed” synthesis of the ...


Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis In A Porcine Model Of Cardiac Ischemia, Anna A. Bulysheva, Barbara Hargrave, Nina Burcus, Cathryn G. Lundberg, Len Murray, Richard Heller Aug 2016

Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis In A Porcine Model Of Cardiac Ischemia, Anna A. Bulysheva, Barbara Hargrave, Nina Burcus, Cathryn G. Lundberg, Len Murray, Richard Heller

Bioelectrics Publications

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility ...


Genetic Diversity In Concentration Of A Protein Subcomponent In Selected Wheat Lines, Andrew B. Berman, Kelsey Gentry, Alexander K. Lee, Molly Yandrofski, Malorie Young, Robert L. Paris Jul 2016

Genetic Diversity In Concentration Of A Protein Subcomponent In Selected Wheat Lines, Andrew B. Berman, Kelsey Gentry, Alexander K. Lee, Molly Yandrofski, Malorie Young, Robert L. Paris

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. 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 would be beneficial to future development of wheat lines with reduced 33 mer concentration. Protein from wheat flour was extracted and subjected to western blot in order to quantify the concentration of 33-mer. This will be a valuable tool for future research efforts focused on identification and ...


The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez Jun 2016

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation of gene ...


Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez May 2016

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 ...


Application Of Genomic Technologies To Study Infertility, Nicholas Rui Yuan Ho May 2016

Application Of Genomic Technologies To Study Infertility, Nicholas Rui Yuan Ho

Arts & Sciences Electronic Theses and Dissertations

An estimated one in eight couples in the United States are diagnosed with infertility. There is a significant genetic contribution to infertility, with estimates of heritability ranging from 0.2 to 0.5. We know surprisingly little about the genetic causes, with only slightly more than a hundred genes known to cause human infertility. I have been translating recent advances in genomics to study infertility in a more efficient manner, in order to improve our knowledge of the genetic causes. By using high throughput genomics and proteomics datasets from other groups, I was able to feed that into a machine ...


The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader May 2016

The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader

Senior Honors Theses

Metabolic disorders affect around thirty-four percent of the population in the United States. Among these disorders is lactose intolerance, which results from diminished production of the human lactase enzyme. This disorder and others like it are genetically determined and cannot be cured. However, the use of transformed bacteria implanted in the colon may provide a means by which the faulty pathway can be bypassed. To test whether transformed bacteria have the capability to aid in the digestion of normally indigestible compounds, a transformed strain of Escherichia coli overexpressing the beta-galactosidase enzyme encoded by the lacZ gene was colonized in the ...


The Role Of Cellulose Synthase-Like D Genes In Tip Growth Of Physcomitrella Patens, Erin E. Killeavy, Arielle Chaves, Alison Roberts May 2016

The Role Of Cellulose Synthase-Like D Genes In Tip Growth Of Physcomitrella Patens, Erin E. Killeavy, Arielle Chaves, Alison Roberts

Senior Honors Projects

Physcomitrella patens is a non-vascular plant with a relatively small genome and is amongst the few eukaryotic organisms that have a high rate of homologous recombination. This is valuable in biological research because it allows for targeted genetic modification of the organism. In vascular plants like Arabidopsis thaliana, a model organism, Cellulose Synthase-like D (CSLD) genes have been discovered to be important in tip growth. This type of growth is observed in the pollen tubes and root hairs of these plant types. The CSLD genes in Arabidopsis were found to play a crucial role in the growth of root hairs ...


The Molecular Basis Of The Genesis Of Basal Tone In Internal Anal Sphincter, Cheng-Hai Zhang, Donghai Lui, Ping Lu, Kaizhi Zheng, Siobhan M. Craige, Lawrence Lifshitz, John F. Keaney Jr., Kevin E. Fogarty, Ronghua Zhuge, Min-Sheng Zhu Apr 2016

The Molecular Basis Of The Genesis Of Basal Tone In Internal Anal Sphincter, Cheng-Hai Zhang, Donghai Lui, Ping Lu, Kaizhi Zheng, Siobhan M. Craige, Lawrence Lifshitz, John F. Keaney Jr., Kevin E. Fogarty, Ronghua Zhuge, Min-Sheng Zhu

Open Access Articles

Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca(2+) channels (VDCCs) or TMEM16A Ca(2+)-activated Cl(-) channels significantly changes global cytosolic Ca(2+) concentration ([Ca(2+)]i) and the tone. TMEM16A deletion in IAS-SMCs abolishes ...


Genetic Diversity In Concentration Of A Protein Subcomponent In Selected Wheat Lines, Andrew B. Berman, Kelsey Gentry, Alexander K. Lee, Molly Yandrofski, Malorie Young, Robert L. Paris Apr 2016

Genetic Diversity In Concentration Of A Protein Subcomponent In Selected Wheat Lines, Andrew B. Berman, Kelsey Gentry, Alexander K. Lee, Molly Yandrofski, Malorie Young, Robert L. Paris

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. 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 would be beneficial to future development of wheat lines with reduced 33 mer concentration. Protein from wheat flour was extracted and subjected to western blot in order to quantify the concentration of 33-mer. This will be a valuable tool for future research efforts focused on identification and ...


Nonreplicative Dna Helicases Involved In Maintaining Genome Stability, Salahuddin Syed Apr 2016

Nonreplicative Dna Helicases Involved In Maintaining Genome Stability, Salahuddin Syed

Graduate Theses and Dissertations

Double-strand breaks and stalled forks arise when the replication machinery encounters damage from exogenous sources like DNA damaging agents or ionizing radiation, and require specific DNA helicases to resolve these structures. Sgs1 of Saccharomyces cerevisiae is a member of the RecQ family of DNA helicases and has a role in DNA repair and recombination. The RecQ family includes human genes BLM, WRN, RECQL4, RECQL1, and RECQL5. Mutations in BLM, WRN, and RECQL4 result in genetic disorders characterized by developmental abnormalities and a predisposition to cancer. All RecQ helicases have common features including a helicase domain, an RQC domain, and a ...


Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung Apr 2016

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic ...


Investigating The Roles And Interactions Of Sad-6 Within The Parameters Of Meiotic Silencing By Unpaired Dna (Msud)., Zachary J. Smith Mar 2016

Investigating The Roles And Interactions Of Sad-6 Within The Parameters Of Meiotic Silencing By Unpaired Dna (Msud)., Zachary J. Smith

Theses and Dissertations

Meiotic silencing by unpaired DNA (MSUD) is a process observed in the model organism Neurospora crassa. During this process unpaired DNA between homologous chromosomes is detected and silenced, resulting in the suppression of unpaired genes. The effects of MSUD can be seen using phenotypic markers such as the Roundspore gene and evidence supports the existence of a physical search for unpaired DNA. However, the mechanism for detecting unpaired DNA remains uncertain. Previously, we have shown evidence that a Rad54-like protein, SAD-6 is required for the efficient completion of MSUD and may be necessary for the detection of unpaired DNA. Currently ...


Staufen Negatively Modulates Microrna Activity In Caenorhabditis Elegans, Zhiji Ren, Isana Veksler-Lublinsky, David Morrissey, Victor Ambros Mar 2016

Staufen Negatively Modulates Microrna Activity In Caenorhabditis Elegans, Zhiji Ren, Isana Veksler-Lublinsky, David Morrissey, Victor Ambros

Victor R. Ambros

The double-stranded RNA-binding protein Staufen has been implicated in various post-transcriptional gene regulatory processes. Here we demonstrate that the Caenorhabditis elegans homolog of Staufen, STAU-1, functionally interacts with microRNAs. Loss-of-function mutations of stau-1 significantly suppress phenotypes of let-7 family microRNA mutants, a hypomorphic allele of dicer and a lsy-6 microRNA partial loss-of-function mutant. Furthermore, STAU-1 modulates the activity of lin-14, a target of lin-4 and let-7 family microRNAs, and this modulation is abolished when the 3' untranslated region of lin-14 is removed. Deep sequencing of small RNA cDNA libraries reveals no dramatic change in the levels of microRNAs, or other ...


Microrna-34a-Mediated Down-Regulation Of The Microglial-Enriched Triggering Receptor And Phagocytosis-Sensor Trem2 In Age-Related Macular Degeneration, Surjyadipta Bhattacharjee, Yuhai Zhao, Prerna Dua, Evgeny I. Rogaev, Walter J. Lukiw Mar 2016

Microrna-34a-Mediated Down-Regulation Of The Microglial-Enriched Triggering Receptor And Phagocytosis-Sensor Trem2 In Age-Related Macular Degeneration, Surjyadipta Bhattacharjee, Yuhai Zhao, Prerna Dua, Evgeny I. Rogaev, Walter J. Lukiw

Psychiatry Publications and Presentations

The aggregation of Abeta42-peptides and the formation of drusen in age-related macular degeneration (AMD) are due in part to the inability of homeostatic phagocytic mechanisms to clear self-aggregating Abeta42-peptides from the extracellular space. The triggering receptor expressed in myeloid/microglial cells-2 (TREM2), a trans-membrane-spanning, sensor-receptor of the immune-globulin/lectin-like gene superfamily is a critical component of Abeta42-peptide clearance. Here we report a significant deficit in TREM2 in AMD retina and in cytokine- or oxidatively-stressed microglial (MG) cells. RT-PCR, miRNA-array, LED-Northern and Western blot studies indicated up-regulation of a microglial-enriched NF-small ka, CyrillicB-sensitive miRNA-34a coupled to a down-regulation of TREM2 in ...


No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon Mar 2016

No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon

UMass Metabolic Network Publications

Previous studies of laboratory strains of budding yeast had shown that when gene copy number is altered experimentally, RNA levels generally scale accordingly. This is true when the copy number of individual genes or entire chromosomes is altered. In a recent study, Hose et al. (2015) reported that this tight correlation between gene copy number and RNA levels is not observed in recently isolated wild Saccharomyces cerevisiae variants. To understand the origins of this proposed difference in gene expression regulation between natural variants and laboratory strains of S. cerevisiae, we evaluated the karyotype and gene expression studies performed by Hose ...


Staufen Negatively Modulates Microrna Activity In Caenorhabditis Elegans, Zhiji Ren, Isana Veksler-Lublinsky, David Morrissey, Victor R. Ambros Feb 2016

Staufen Negatively Modulates Microrna Activity In Caenorhabditis Elegans, Zhiji Ren, Isana Veksler-Lublinsky, David Morrissey, Victor R. Ambros

Program in Molecular Medicine Publications and Presentations

The double-stranded RNA-binding protein Staufen has been implicated in various post-transcriptional gene regulatory processes. Here we demonstrate that the Caenorhabditis elegans homolog of Staufen, STAU-1, functionally interacts with microRNAs. Loss-of-function mutations of stau-1 significantly suppress phenotypes of let-7 family microRNA mutants, a hypomorphic allele of dicer and a lsy-6 microRNA partial loss-of-function mutant. Furthermore, STAU-1 modulates the activity of lin-14, a target of lin-4 and let-7 family microRNAs, and this modulation is abolished when the 3' untranslated region of lin-14 is removed. Deep sequencing of small RNA cDNA libraries reveals no dramatic change in the levels of microRNAs, or other ...


Genomic Analysis Of Meiothermus Ruber Mrub_1907 And Meiothermus Ruber Mrub_1844 With Potential Ortholog Escherichia Coli B3774 Ilvc And Escherichia Coli B3771 Ilvc Gene Through Bioinformatics, Felipe A. Hernandez, Dr. Lori Scott Feb 2016

Genomic Analysis Of Meiothermus Ruber Mrub_1907 And Meiothermus Ruber Mrub_1844 With Potential Ortholog Escherichia Coli B3774 Ilvc And Escherichia Coli B3771 Ilvc Gene Through Bioinformatics, Felipe A. Hernandez, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_1907 and Mrub_1844. We predict that Mrub__1907 encodes the enzyme ketol-acid reductoisomerase (DNA coordinates 1966630..1967649 on the reverse strand), which is the fourth step of the L-isoleucine pathway (from threonine) (KEGG map number 00290). It catalyzes the conversion of (R)-3- Hydroxy-3-methyl-2-oxopentanoate to (R)-2-3 Dihydroxy-3-methylpentanoate. The E. coli K12 MG1655 ortholog is predicted to be b3774, which has ...


E. Coli B3639 And B3634 Are Orthologs Of Mrub_2047 And Mrub_1372, Rong Zheng, Dr. Lori Scott Feb 2016

E. Coli B3639 And B3634 Are Orthologs Of Mrub_2047 And Mrub_1372, Rong Zheng, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2047 and Mrub_1372. We predict that Mrub_2047 encodes the enzyme fused 4'-phosphopantothenoylcysteine decarboxylase/phosphopantothenoylcysteine synthetase, FMN-binding (DNA coordinates 2083590..2084816 on the forward strand), which is the first and the second steps of the CoA biosynthesis pathway (KEGG map number 00770). It catalyzes the conversion of (R)-4’-phosphopantothenate to (R)-4’-phosphopantothenoyl-L-cysteine and the conversion of (R)-4 ...


Comparing Meiothermus Ruber And Myxococcus Xanthus In The Purine Metabolism Pathway, Linnea J. Ritchie, Dr. Lori Scott Feb 2016

Comparing Meiothermus Ruber And Myxococcus Xanthus In The Purine Metabolism Pathway, Linnea J. Ritchie, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. I investigated the biological functions of Mrub_1053 Mrub_2281 and Mrub_2299. I predicted that Mrub_1053 and Mrub_2281 (DNA coordinates 1053364..1054359 on the forward strand and 2333172..2334113 on the forward strand respectively) encodes the enzyme phosphoribose-1-pyrophosphate synthetase (PRS) which is the first step of the purine synthesis pathway (KEGG). I also predicted that Mrub_2299 (DNA coordinates: 2352378..2353775 on the forward strand) encodes for Phosphoribosyl pyrophosphate (PRPP) amidotransferase ...


Dna Sequencing Activity, Sarah O'Leary-Driscoll Feb 2016

Dna Sequencing Activity, Sarah O'Leary-Driscoll

Sequencing & Genome Mining

This activity is meant to introduce students to basic DNA sequencing techniques. Using a hands-on approach helps them understand the fundamentals of what is happening in the lab, and the questions that accompany the activity can lead to more in depth discussions about sequencing, and the development of the next generation sequencing techniques.


An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu Jan 2016

An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone ...


A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi Jan 2016

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly ...


Letter From The Dean, Lona Robertson Jan 2016

Letter From The Dean, Lona Robertson

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

No abstract provided.


On The Molecular Biology And Evolution Of Plant Parasitism By Nematodes, Jason Brett Noon Jan 2016

On The Molecular Biology And Evolution Of Plant Parasitism By Nematodes, Jason Brett Noon

Graduate Theses and Dissertations

Plant-parasitic nematodes (PPN) are among the most devastating plant pathogens. However, our understanding of how nematodes adapted to plant parasitism, and the molecular mechanisms that PPN use during infection is limited. Among the most important genomic changes that occurred in the free-living nematode ancestors of PPN were multiple horizontal gene transfer (HGT) events from bacteria. Though it is clear that HGT helped shape the genomes of many PPN, how this process occurred is unknown. Also, it is evident that successful parasitism occurs from the delivery of proteinaceous effectors into plant roots to hijack and modify host cellular processes.

The research ...


Centromere Identity And The Nature Of The Cenp-A-Containing Nucleosome, Samantha Jane Falk Jan 2016

Centromere Identity And The Nature Of The Cenp-A-Containing Nucleosome, Samantha Jane Falk

Publicly Accessible Penn Dissertations

The centromere is an essential chromosomal locus that serves as the site of kinetochore formation, ensuring accurate chromosome segregation during mitosis and meiosis. While most centromeres form on repetitive DNA, the underlying DNA sequence is neither necessary nor sufficient to support centromere function, suggesting that this locus is epigenetically defined. The histone H3 variant centromere protein A (CENP-A) replaces H3 in nucleosomes at the centromere and is the best candidate to provide this epigenetic mark. This thesis aims to understand the features of the CENP-A nucleosome that impart its ability to mark and stabilize functional centromeres. In the first part ...


The Mitotic Genome: Accessibility And Transcriptional Control, Chris Hsiung Jan 2016

The Mitotic Genome: Accessibility And Transcriptional Control, Chris Hsiung

Publicly Accessible Penn Dissertations

Mitosis entails dramatic global alterations to genome structure and regulation, including

chromosome condensation, dissociation of the transcriptional machinery from chromosomes, and transcriptional silencing. Here I report studies that address the macromolecular accessibility of the mitotic genome and the control of transcriptional reactivation upon mitotic exit in a mammalian cell line. The results obtained from measuring the sensitivity of chromatin to DNase I cleavage by sequencing (DNase-seq) in pure mitotic cell populations demonstrate that macromolecular accessibility of the mitotic genome is widely preserved. Thus, steric hindrance from chromatin condensation is insufficient for explaining the eviction of transcription factors from mitotic chromatin ...