Molecular Genetics Commons^™

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

Evolutionary Linkage Of Mimetic And Non-Mimetic Color Traits In A Coral Snake Mimicry Complex, John D. Curlis Jr

College of Graduate Studies: Theses & Dissertations

Color polymorphism in aposematic mimicry systems is a perplexing phenomenon for evolutionary biologists, as theoretically the benefits of converging on a model phenotype should constrain the evolution of phenotypic diversity in these systems (i.e., color polymorphism should not occur). Nevertheless, color polymorphism in mimicry systems is prevalent throughout many taxa. In some of these systems, the evolution of color polymorphism results in the existence of non-mimetic morphs, such as those that are cryptic. The case of ground snakes (Sonora semiannulata) is unique in that color polymorphism encompasses both mimetic and cryptic morphs, as well as individual mimetic and …

Transcriptomic Analyses Of Cathatranthus Roseus Hairy Roots Overexpressing Crmyc2 And Orca3 And Roles Of Cross-Family Transcription Factor Interaction In Terpenoid Indole Alkaloid Biosynthesis, Xueyi Sui

Theses and Dissertations--Plant and Soil Sciences

Catharanthus roseus (Madagascar periwinkle), is a well-known medicinal plant that produces a vast array of terpenoid indole alkaloids (TIAs), including two anticancer compounds vinblastine and vincristine. Industrial scale production of TIAs is hampered by the difficulties of total chemical synthesis of these compounds and the fragmented knowledge on TIA pathway. Transcriptional regulation of the TIA biosynthetic pathway has not been thoroughly investigated in Catharanthus and only a few structural genes have been identified as the targets of two master regulators: the basic helix-loop-helix (bHLH) transcription factor (TF) CrMYC2 and APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF), ORCA3. Next generation sequencing (NGS) has been …

A Phylogenetic And Environmental Analysis Of Brazilian Placosoma Lizards, Kai A. Farje-Van Vlack

Dissertations and Theses

Placosoma is a genus comprised of the Brazilian spectacled lizards P. champsonotus, P. cipoense, P. cordylinum, P. glabellum, and P. limaverdorum. While P. champsonotus, P. cordylinum, and P. glabellum occupy the southern coast of Brazil, P. cipoense is found in the montane grasslands north of that range, and P. limaverdorum was recently discovered in forest isolates that persist within the semi-arid Caatinga. This study elucidates the ecological and evolutionary relationships among these morphologically similar lizards. Using mitochondrial and nuclear gene sequences, genus-wide phylogenies were inferred through Bayesian inference and a species tree approach, …

Taf2: A Potential Oncogene For Hepatocellular Carcinoma, Saranya Chidambaranathan Reghupaty

Theses and Dissertations

Astrocyte Elevated Gene 1 (AEG1) is an oncogene for hepatocellular carcinoma (HCC). Its role in HCC pathogenesis has been well studied. A pan cancer analysis of gene expression in multiple databases identified TATA-box binding protein associated factor 2 (TAF2) as the gene that is most frequently co-expressed with AEG1. TAF2 is a protein that is involved in transcription of genes by RNA polymerase II. It is a factor that is dispensable for basal transcription but, required for activated transcription. It has also been shown to be involved in regulating cyclin levels and hence cell cycle progression. Bioinformatic analysis on data …

Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan

Theses and Dissertations

DNA methylation is necessary for learning, memory consolidation and has been implicated in a number of neuropsychiatric disorders. Obtaining high quality and comprehensive data for the three common forms of methylation in brain is challenging for methylome-wide association studies (MWAS). To address this we optimized a panel of enrichment methods for screening the brain methylome. Results show that these enrichment techniques approach the coverage and fidelity of the current gold standard bisulfite based techniques. Our MBD-based method can also be used with low amounts of genomic material from limited human biomaterials. Psychiatric disorders have high prevalence and are often chronic …

Pnpase In C. Elegans: Mutagenic Analysis To Complement Knockdown Studies, Danielle K. Seibert

Theses and Dissertations

PNPase is a gene implicated as a potential target for cancer therapy; human mutations also present with deafness, myopathies, and neuropathies. In this study, C. elegans was used to investigate the effect of knocking out PNPase in a whole animal. C. elegans knockdown studies have reported an extended lifespan via an increase in ROS production. Further noted are larger mitochondria and an increase in fzo-1 expression. Knockout animals previously constructed using CRISPR/Cas9 were used for this study. We aimed to confirm these findings validating previous studies. It was discovered that PNPase knockout animals demonstrated a similar lifespan extension that was …

Characterization Of Staphylococcal Nuclease And Tudor Domain Containing Protein 1 (Snd1) As A Molecular Target In Hepatocellular Carcinoma And Non-Alcoholic Steatohepatitis, Nidhi H. Jariwala

Theses and Dissertations

CHARACTERIZATION OF STAPHYLOCOCCAL NUCLEASE AND TUDOR DOMAIN CONTAINING PROTEIN 1 (SND1) AS A MOLECULAR TARGET IN HEPATOCELLULAR CARCINOMA AND NON-ALCOHOLIC STEATOHEPATITIS

Nidhi Jariwala, PhD

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Integrative Life Sciences

Virginia Commonwealth University, 2017

Devanand Sarkar, M.B.B.S., PhD.

Associate Professor, Department of Human and Molecular Genetics

Virginia Commonwealth University

Richmond, Virginia

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). Oncoprotein SND1 regulates gene expression at a post-transcriptional level in multiple cancers including hepatocellular carcinoma (HCC). …

Detection Of Antibiotic Resistance Loci In Wastewater And Fresh Water Samples, Mohammed Hamed Almalki

Masters Theses

Proper treatment of municipal wastewater is important not only for prevention of eutrophication but also for public health concerns. One consideration for wastewater treatment is the presence of organisms carrying antibiotic resistance genes. If these organisms survive the wastewater treatment process and are released into the streams, they can pose significant risks to public health. In addition, their presence also raises concerns for lateral gene transfer events at the wastewater plant. The spread of antibiotic loci has a major impact in public health and clinical therapy because resistant organisms render conventional treatments of important illnesses difficult. Beta-lactam drugs are known …

Effects Of Posttranslational Modification Of Transcription Factor Gli-Similar 3 By Sumoylation On Insulin Transcription In Pancreatic Β Cells, Tyler M. Hoard

Murray State Theses and Dissertations

The ability to control blood glucose levels is a fundamental component of vertebrates. In these organisms, blood glucose homeostasis is achieved through a fine-tuned mechanism that largely involves the secretion of hormones from the endocrine pancreas into the bloodstream. These hormones include glucagon, which is secreted by the α cells of the pancreas and initiates the release of glucose into the bloodstream through gluconeogenesis in the liver, and insulin, which is secreted from the β cells and signals the uptake of excess blood glucose by the peripheral tissue. Gli-similar 3 (Glis3) is a transcription factor that has previously been shown …

¬Multilocus Phylogeny Of The Lichen Family Megasporaceae, Tim B. Wheeler

Graduate Student Theses, Dissertations, & Professional Papers

The lichen symbiosis is one of the oldest studied mutualisms; in fact, Frank and De Bary coined the term "symbiosis" while studying lichens (Frank, 1877; De Bary 1879). The widespread, stable association between the mycobiont and photobiont in lichens offers an ideal system for the study of co-evolution. The recent application of molecular data to lichens has begun to unveil the complexities involved in these associations (Upreti et al. 2015, Spribille et al. 2016). Lichenized fungi make up a huge fraction of fungal diversity (Nash 2008), yet very little is known of their genetic diversity. Fungal taxonomy is notoriously difficult …

Feasibility & Discovery Using Fox System To Generate Gain-Of-Function Mutations With Hybrid Poplars, James Rauschendorfer

Dissertations, Master's Theses and Master's Reports

The Full-length complementary DNA OvereXpression (FOX) system is an approach to generating gain-of-function (GF) plants predominantly used for studying Arabidopsis. This approach inserts T-DNAs containing random full-length complementary DNA (fl-cDNA) with upstream promoter and downstream terminator into the host plant genome. Studies using this method report the success generating overexpression populations with high mutation rates. We choose to investigate the feasibility and effectiveness of this method using poplars. We suspected using a succulent xylem specific fl-cDNAs library would enrich the transformant poplars with mutants affected in traits specific to woody tissue development. We observed a characteristically high mutation rate …

Characterization Of Genic Microsatellite Markers (Est-Ssrs) In The Endangered Oak Species Quercus Georgiana M.A.Curtis, Priyanka Dipak Kadav

Dissertations, Master's Theses and Master's Reports

Quercus is important ecologically and economically because it provides food and habitat for wildlife, wood and paper products for humans. Oaks are endangered due to various factors like shifting climates, habitat loss, drought, pathogens and genetic swamping. Quercus georgiana (M.A. Curtis) is an endangered and restricted oak species which is remaining only in the southeastern part of the US. Efforts are required to conserve this endangered species from extinction. Conservation of this species can be done through these methods: ex-situ conservation (arboretum and botanical garden) and in-situ conservation strategies which protect the species in its natural habitat. For this conservation …

Neutral And Adaptive Genetic Variation In North American Hardwood Tree Species, Sudhir Khodwekar

Dissertations, Master's Theses and Master's Reports

'Northern Hardwoods,’ are a characteristic composition of multiple tree species and a part of the rich and diverse northeastern forests. Hardwoods e.g. oaks (Quercus: Fagaceae and Sugar maple), serve as foundation species and offer ecological and economical gains to wildlife and humans. Most of the forest trees go through many biotic and abiotic stresses, for example climate change in their long life span. To overcome these threats and to adapt to changing conditions, tree species need to maintain variation especially in adaptive genes. Therefore, it is necessary to analyze genetic diversity within forest tree populations and take appropriate …

Cullin-4 Regulates Wingless And Jnk Signaling-Mediated Cell Death In The Drosophila Eye., Meghana Tare, Ankita Sarkar, Shimpi Bedi, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood. In a gain-of-function screen, we found that misexpression of cullin-4 (cul-4), an ubiquitin ligase, can rescue reduced eye mutant phenotypes. Previously, …

The Fate Of Icd-1 During Misfolded Protein Induced Apoptosis In Caenorhabditis Elegans, Kyle H. Perez

Senior Honors Projects, 2010-2019

Severe misfolded protein stress initiates cellular responses that often result in the death of the affected cell, typically by apoptosis. An essential aspect of apoptosis is caspase-mediated cleavage of proteins that, once cleaved, further propagate death. One heterodimeric structure putatively targeted in this process in the nascent polypeptide-associated complex (NAC), a translational chaperone thought to help prevent misfolded protein stress in the ER. The purpose of this investigation was to determine whether the beta subunit of the NAC in C. elegans (ICD-1) is cleaved during the induction of apoptosis, with the hypothesis that ICD-1 is cleaved during stressed-induced apoptosis to …

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 Bioinformatics Methodology For The Annotation And Analysis Of Sperm Chromatin Remodeling Proteins In Sequenced Drosophila Species, Zain A. Alvi

Seton Hall University Dissertations and Theses (ETDs)

Spermatogenesis is the process by which mature functional spermatozoa are formed, and is initiated in the stem cell niche of the testes. During the post-meiotic stage of spermatogenesis, spermiogenesis, transition proteins facilitate the transformation of chromatin from a histone-based nucleosome structure to a protamine-based nucleosome structure. This study is aimed at analyzing genomic, transcript, and protein sequences of transition proteins in 13 sequenced Drosophila species. The Drosophila melanogaster spermatid specific transition protein-like protein (Tpl^94D) was used as the reference sequence in this study. An extensive bioinformatics approach was employed in establishing the Tpl^94D orthologs. We identified …

Punctuated Evolution Within A Eurythermic Genus (Mesenchytraeus) Of Segmented Worms: Genetic Modification Of The Glacier Ice Worm F1f0 Atp Synthase, Shirley A. Lang

Graduate School of Biomedical Sciences Theses and Dissertations

Segmented worms (Annelida) are among the most successful animal inhabitants of extreme environments worldwide. An unusual group of Mesenchytraeus worms endemic to the Pacific Northwest of North America occupy geographically proximal ecozones ranging from low elevation temperate rainforests to high altitude glaciers. Along this altitudinal transect, Mesenchytraeus representatives from disparate habitat types were collected and subjected to deep mitochondrial and nuclear phylogenetic analyses. Evidence presented here employing modern bioinformatic analyses (i.e., maximum likelihood, Bayesian inference, multi-species coalescent) supports a Mesenchytraeus “explosion” in the upper Miocene (5-10 million years ago) that gave rise to ice, snow and terrestrial worms, derived from …

Functional Significance Of Branch Points In Mirtrons, Britton A. Strickland

Honors Theses

MicroRNAs are a heterogeneous group of small regulatory RNAs generated by many pathways. Mirtrons (miR) are a class of microRNAs produced by splicing, and some mirtrons contain a 3’ tail located downstream from the self-complementary hairpin. During RNA splicing, a loop-like “lariat” intermediate structure is created when the 5’ end of the RNA is attached to an adenine called the branch point. The goal of this project is to uncover the contribution of branch point location to the processing of tailed mirtrons into functional gene regulators. This project approaches this issue from two directions. First, branch points were identified by …