Genetics and Genomics Commons^™

Nmr Solution Structures Of Runella Slithyformis Rna 2'-Phosphotransferase Tpt1 Provide Insights Into Nad+ Binding And Specificity, Sébastien Alphonse, Ankan Banerjee, Swathi Dantuluri, Stewart Shuman, Ranajeet Ghose

Publications and Research

Tpt1, an essential component of the fungal and plant tRNA splicing machinery, catalyzes transfer of an internal RNA 2′-PO₄ to NAD⁺ yielding RNA 2′-OH and ADP-ribose-1′,2′-cyclic phosphate products. Here, we report NMR structures of the Tpt1 ortholog from the bacterium Runella slithyformis (RslTpt1), as apoenzyme and bound to NAD⁺. RslTpt1 consists of N- and C-terminal lobes with substantial inter-lobe dynamics in the free and NAD⁺-bound states. ITC measurements of RslTpt1 binding to NAD⁺ (K_D ∼31 μM), ADP-ribose (∼96 μM) and ADP (∼123 μM) indicate that substrate affinity is determined primarily by …

Zebrafish (Danio Rerio) Hoxb6: An Exploration Into The Divergence Of Genomic Dna Sequence And Gene Expression Across Teleost Fishes Post-Genome Duplication, Amber Lynn Rittgers, Pierre Le Pabic, Adam Davis

Georgia Journal of Science

Hoxb6 is an evolutionarily conserved developmental regulatory gene that functions, in part, to pattern several organs and organ systems within the embryonic trunk during vertebrate embryogenesis. The cis-regulatory circuitry mediating trunk expression in mouse (Mus musculus) may be conserved across gnathostome vertebrates, as several other species show similar trunk expression patterns, including chicken (Gallus gallus), dogfish shark (Scyliorhinus canicula), and several teleost fishes. A whole genome duplication event that occurred in the lineage leading to teleost fishes has generated at least two Hoxb6 genes, hoxb6a and b6b. Two teleost fishes of the …

Nanopore Guided Regional Assembly, Eleni Adam, Desh Ranjan, Harold Riethman

College of Sciences Posters

The telomeres are the “caps” of the chromosomes and their vital role is to protect them. Possible telomere dysfunction caused by telomere rearrangements can be fatal for the cell and result in age-related diseases, including cancer. The telomeres and subtelomeres are regions that are hard to investigate. The current technology cannot provide their complete sequence, instead the DNA is given in multiple pieces. Current methods of assembling the pieces of these regions are not accurate enough due to the region’s high variability and complex repeated patterns. We propose a hybrid assembly method, the NPGREAT, which utilizes two of the latest …

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …

Determining Master Regulatory Genes Of Muscle Senescence In The Hawk Moth, Manduca Sexta, Leah J. Naasz

Honors Thesis

ABSTRACT DETERMINING MASTER REGULATORY GENES OF MUSCLE SENESCENCE IN THE HAWK MOTH, MANDUCA SEXTA Leah Naasz Director: Bernie Wone, Ph.D. Skeletal muscle exhibits a gradual deterioration of its functional capabilities as it senesces. While the adverse effects of muscle aging are well-known, the molecular trigger of this degenerative process is unknown. Here, I aim to identify master regulatory genes (i.e., transcription factors) that might be involved in the initiation of the muscle senescence process in our muscle aging model Manduca sexta. This invertebrate adult moth was chosen as the model organism due to its relatively short lifespan, similarity to the …

Genomic Studies Of Beaf-32 In Drosophila, John Keller Mckowen Iii

LSU Doctoral Dissertations

Compared to humans, the model organism Drosophila melanogaster is particularly gene dense and encodes several insulator binding proteins (IBP) to aid in its genome organization. Our focus of research is a particular IBP, Boundary Element-Associated Factor of 32kD (BEAF). BEAF primarily binds near the promoters of constitutively active housekeeping genes. It is thought to help maintain the active state of these genes by preventing the spread of repressive chromatin. Additionally, the enhancer blocking activity of BEAF is thought to prevent aberrant activation or silencing of genes. BEAF appears to be ubiquitously expressed among cells and tissues, albeit at varying levels. …

Phenotypic Characters And Expression Of Cytokinin Oxidase 2 (Osckx2) Gene In Rice Genotypes With Enhanced Grain Filling Traits, Cielo Luz C. Mondejar, Maria Genaleen Q. Diaz, Teresita H. Borromeo, Tonette P. Laude, Arlen A. Dela Cruz, Roel Rodriguez Suralta

The Philippine Agricultural Scientist

Poor grain filling is still a major problem in rice production. Recent attention in crop varietal improvement is focused on heritable delayed foliar senescence, enhanced root system, and fast-synchronous grain filling pattern. Nine genotypes were characterized for these three enhanced grain-filling traits to determine the role of these traits on grain yield. Based on heritable delayed foliar senescence, NSIC Rc436 and NSIC Rc512 were characterized as Type A, while PSB Rc18 and NSIC Rc514 as Type B. These genotypes had a significantly higher yield than IR64, owing to their high spikelets number. Data suggested a positive correlation between the delayed …

The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle

Honors College Theses

Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …

Expression And Function Of Transcription Factors Foxa1, Hoxb13 And Cdx2 In Prostate Cancer, Hamsat B. Anwar

University Honors Theses

Prostate cancer (PC) is the second leading cause of death in men, affecting around 190 thousand patients in 2020 alone (National Institute of Cancer, 2020). Much of the current research focuses on treatments for advanced PC, which is problematic due to the rapid evolution of tumors and development of treatment resistance. Cancer early detection presents a better approach to control and treat patients before they acquire an incurable disease. Earlier diagnosis of patients leads to better prognosis and a more comfortable treatment process (Etzioni et al., 2003). However, we currently lack molecular markers to stratify PC during its early stages. …

Synthesis, Structure-Activity Relationships, And Antiviral Activity Of Allosteric Inhibitors Of Flavivirus Ns2b-Ns3 Protease, Shenyou Nie, Yuan Yao, Fangrui Wu, Xiaowei Wu, Jidong Zhao, Yuanda Hua, Jingyu Wu, Tong Huo, Yi-Lun Lin, Alexander R Kneubehl, Megan B Vogt, Josephine Ferreon, Rebecca Rico-Hesse, Yongcheng Song

Faculty, Staff and Students Publications

Flaviviruses, including Zika, dengue and West Nile virus, are important human pathogens. The highly conserved NS2B-NS3 protease of Flavivirus is essential for viral replication and therefore a promising drug target. Through compound screen followed by medicinal chemistry studies, a novel series of 2,5,6-trisubstituted pyrazine compounds are found to be potent, allosteric inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 130 nM. Their structure-activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile virus and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus …

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha

Publications and Research

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). …

Utilizing Plastic-Degrading Microbes For Plastic Degradation, Brandon Garcia

Global Sustainable Development Projects

Our oceans are full of pollution and a large portion of those are plastics. They resist degradation from the elements and have long half-lives. About 300 million metric tons of plastic are dumped into our oceans every year. Many of these include polyethylene (PE), polypropylene (PP), polystyrene (PS), etc. Much of this is not recycled and so there is a massive accumulation of it present in our oceans. Microbes tend to form biofilms on these plastics and break them down. However, the relationship between plastics and the diversity of biofilm communities are being understood as well as how we can …

Role Of Na/K-Atpase Non-Enzymatic Signaling In Renal Proximal Tubule Sodium Transport, Shreya Tapan Mukherji

Theses, Dissertations and Capstones

The renal proximal tubule (RPT) is the center stage for renal handling of Na+ , a potent determinant of systemic Na+ and volume homeostasis in health and disease. In the RPT, through its classic ion-pumping function, Na + /K+ -ATPase (NKA) generates the Na+ gradient that drives apical Na+ absorption, mostly through Na+ /H+ exchanger (NHE3). In contrast, pharmacological evidence suggests that the activation of the NKA non-enzymatic signaling function, through Src and other signaling partners, triggers a cellular redistribution of NKA and NHE3 that decreases transcellular Na+ flux in cultured RPT cells. However, the physiological relevance of the nonenzymatic …

We Achieved Efficient Gene Editing In Zebrafish Using A Two-Part Rna Crispr-Cas9 System, Kyrian Carley, Daniel Sculley, Emma Pastoor, Valeria Lacroix, Ashley Meyer, Brianna Jansen, Joshua Deyoung, Rachael Baker, Amy Wilstermann

Summer Research

• Establish effective protocols for using CRISPR-Cas9 technology with the equipment we have in our lab.
• Create a zebrafish model of BCS1L mutations to better elucidate genotype-phenotype connections.

The Study Of Ppal And Its Role In The Development Of Physcomitrella Patens, Susana Perez-Martinez, Christine Chen, Mark P. Running

Undergraduate Arts and Research Showcase

Protein Prenylation is the addition of lipids to select proteins that play a key role during the development of plants. There are three enzymes that play a role in protein prenylation: protein farnesyltransferase (PFT), protein geranylgeranyl-transferase-I (PGGT), and Rab geranylgeranyltransferase (Rab-GGT). However, there is a protein called PPAL that has a similar alpha subunit of PFT, PGGT, and RAB-GGT but its biochemical function is unknown. Physconmitrella patens, a type of moss, was chosen to explore the role of PpPPAL in the development process. There are two copies of PPAL found in moss. PPAL1 and PPAL2. To study the role …

Disease Prevalence And The Population Genetic Structure Of Crassostrea Virginica Along The Georgia Coast, Sarah Batchelor

College of Graduate Studies: Theses & Dissertations

The Eastern Oyster, Crassostrea virginica, is an ecologically important species that plays a role in protecting shorelines, water filtration, and providing habitat and food for various fish species. Perkinsus marinus and Haplosporidium nesloni are two pathogens currently affecting oyster populations. These pathogens have both been documented as causes of mass mortality events along the East coast. They greatly diminish the health of oysters, resulting in the degradation of oyster tissue, reduction in growth and reproductive ability, and may cause death. In this study, wild oysters were collected from eleven locations along the Georgia coast to investigate the presence, intensity, …

Vasculogenic Mimicry: Role Of Melanoma Differentiation Associated Gene-9/Syntenin, Jinkal Modi, Anjan Pradhan, Luni Emdad, Swadesh Das, Paul Fisher

Graduate Research Posters

Malignant melanoma (MM) is the most aggressive skin cancer and the most frequent skin disorder in Caucasians. MM is associated with aggressive and progressive disease states, leading to major cancer-related morbidity and mortality. Recent investigations identify a new non-angiogenesis-dependent pathway vasculogenic mimicry (VM), which is considered a cancer hallmark that can independently facilitate tumor neovascularization by the formation of fluid-conducting and vascular endothelial cells. MM cells undergoing VM can dedifferentiate into numerous cellular phenotypes and acquire endothelial-like features, resulting in the formation of the de novo matrix-rich vascular-like network, such as plasma and red blood cells. The co-generation of endothelial …

Principal Components Analysis Corrects Collider Bias In Polygenic Risk Score Effect Size Estimation, Nathaniel S. Thomas, Peter B. Barr, Fazil Aliev, Sally I. Kuo, Danielle M. Dick, Jessica E. Salvatore

Graduate Research Posters

BACKGROUND: Genome-wide polygenic scoring has emerged as a way to predict psychiatric and behavioral outcomes and identify environments that promote the expression of genetic risks. An increasing number of studies demonstrate that the effects of polygenic risk scores (PRS) may be biased by the inclusion of heritable environments as covariates when the environment is influenced by unmeasured confounding variables, an example of collider bias. Inclusion of the principal components of observed confounders as covariates may correct for the effect of unmeasured confounders.

METHODS: A simulation study was conducted to test principal components analysis (PCA) as a correction for collider bias. …

Mechanisms Of Cadmium-Induced And Epidermal Growth Factor Receptor Mutation-Driven Lung Tumorigenesis, Hsuan-Pei Lin

Theses and Dissertations--Toxicology and Cancer Biology

Cadmium (Cd) is a ubiquitous pollutant in the environment and a known carcinogen for lung cancer. Cd has been shown to act as a weak mutagen, which suggests that it may exert tumorigenic effect through non-genotoxic ways, such as epigenetic mechanisms. The goal of this project is to investigate the mechanisms of Cd carcinogenesis focusing on the role of lncRNA dysregulations. The Cd-exposed cells formed significantly more colonies in soft agar, displayed cancer stem cell (CSC)-like property and formed tumors in nude mice. Mechanistically, the lncRNA microarray analysis revealed that chronic Cd exposure dysregulates lncRNA expressions. Q-PCR analysis confirmed the …

Functional Analysis Of Folate Biosynthesis Genes Of Rickettsia Monacensis Str. Humboldt Via Complementation Assay, Brandon James Hill

Cal Poly Humboldt theses and projects

Nutritive symbiosis between bacteria and ticks is observed across a range of microbes and hosts, however, little characterization on the molecular components responsible for these symbioses has been done. Previous studies in our lab demonstrated that Rickettsia monacensis str. Humboldt (RMSH) can synthesize folate de novo via folA, folC, folE, folKP, and ptpS pathway. In this study expression of RMSH folate genes within a folate gene mutant E. coli K-12 strain BW25113 was used to functionally characterize RMSH folate genes in vivo. RMSH folate genes were subcloned into TransBac vector and transformed into folA, …

Genome-Wide Characterization Of Lateral Organ Boundaries Domain Genes In Sunflower (Helianthus Annuus L.), Saleh M. Aljurbua

Masters Theses

Lateral Organ Boundaries (LBD) gene family encodes transcription factors found only in plants with essential roles in growth, development, and response to biotic and abiotic factors. The sunflower (Helianthus annuus L., Asteraceae family) LBD genes were studied using different in silico and phylogenetic approaches including four major steps: gene identification, phylogenic analysis, structural analysis, and expression analysis. Sixty-four sunflower LBD genes (HaLBDs) were identified using query search of all Arabidopsis LBD genes against sunflower genome (version r1.2) followed by LBD domain sequence verification. A phylogenetic tree was reconstructed using MEGA-X program. The identified genes were phylogenetically classified into two main …

Slowing Down The Clock: Cellular Senescence And Aging, Saad Bhatti

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

No abstract provided.

Composition And Homology In The Taxonomic Classification Of Escherichia Coli, Tanya Irani

Theses and Dissertations (Comprehensive)

As new techniques have been introduced, specifically the possibility of complete genome sequencing, better methods of defining bacterial species have also been proposed. One of the most recently proposed methods, using bioinformatic techniques, is to calculate the average nucleotide identity (ANI) between the homologous genome segments of different isolates. Another method for species discrimination that has been tested successfully is the similarity of DNA compositional signatures. However, in a recent update, DNA signatures split the available Escherichia coli complete genomes into three groups. To check if this result was consistent with such genomes belonging to different species, we tested methods …

Using Genetics In A Model Organism To Understand Polyamine Transport, Victoria A. Millington

Honors Undergraduate Theses

Polyamines are small positively charged molecules that control major vital cellular processes including cell growth and proliferation, gene expression, protein production and cell death. Cells can obtain polyamines by making them (biosynthesis) or bringing them into the cell from the outside (transport). Cancer cells require high levels of polyamines to sustain their rapid growth, and depletion of polyamines slows the growth of malignant cells. An FDA approved drug, difluoromethylornithine (DFMO), blocks biosynthesis but is often ineffective because tumor cells respond by increasing transport of polyamines. Thus, a dual therapy that simultaneously targets polyamine biosynthesis and transport is needed. The mechanism …

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Genetic Mouse Models Of Liver Disease: Potential Roles Of Zhx2 (Afr1) And Afr2 In Damage And Regeneration, Courtney P. Turpin

Theses and Dissertations--Pharmacology and Nutritional Sciences

The liver is the largest internal organ in mammals and responsible for carrying out various processes, including lipid and carbohydrate metabolism, detoxification of chemicals, and production of serum proteins. Liver damage, which can be caused by a variety of agents including viral infection, environmental toxins, alcohol and excessive dietary fats, can cause dysregulation of these critical functions, leading to worsening liver pathophysiology and impacting health. However, the liver has the remarkable ability to regenerate when damaged. Hepatocytes, which comprise a majority of liver cells, are relatively quiescent under healthy conditions. Upon injury, remaining hepatocytes can proliferate to recover from liver …

Southern Pine Beetle-Specific Rna Interference Demonstrates No Effects On Nontarget Insects, Hannah Marie Hollowell

Theses and Dissertations--Entomology

The endemic southern pine beetle (SPB), Dendroctonus frontalis Zimmermann, is a highly destructive bark beetle that has devastated coniferous forests of the southern United States for decades. Traditional management strategies have been unable to respond effectively to largescale SPB outbreaks, prompting exploration of novel techniques including RNA interference (RNAi). Double-stranded RNAs (dsRNAs) are effective at triggering gene silencing and inducing mortality in SPB, but determining delivery methods and demonstrating specificity of the treatments is necessary before this technology may progress to deployment.

I evaluated three SPB-specific dsRNAs on model nontarget insects to assess potential lethal effects, sublethal effects such as …

Functional Genetic Approaches To Provide Evidence For The Role Of Toolkit Genes In The Evolution Of Complex Color Patterns In Drosophila Guttifera, Mujeeb Olushola Shittu

Dissertations, Master's Theses and Master's Reports

Toolkit genes are set of genes that orchestrate the development of basic body plan of animals, and they are highly conserved in all animals. The co-option of the toolkit genes into the pigmentation pathway has led to the evolution of novel species. This study focuses on understanding how the complex color patterns in animals develop by using the Drosophila species in the quinaria group as models. We developed an mRNA in situ hybridization (ISH) protocol, which allowed us to study gene expression patterns in the abdomen of developing pupae of non-model Drosophila species (Chapter 2). Through ISH, we found that …

Transactivation And Mitochondrial Activity Are Affected By High Temperature In C. Elegans Sperm, Jacqueline Mcvay

Scripps Senior Theses

Sexual reproduction has a conserved flaw in that it is temperature sensitive. Exposure to high temperature leads to male infertility, but little is known about the underlying mechanism. Understanding these mechanisms is important for agriculture and reproductive medicine. Using C. elegans, we investigated two potential aspects of male fertility that may be affected by high temperature conditions: activation of sperm by seminal fluid and sperm mitochondrial activity. There are two pathways for sperm activation in C. elegans: the SPE-8 pathway in hermaphrodites and the TRY-5 pathway in male seminal fluid. Hermaphrodite sperm with a mutation in spe-8 can …