Genetics Commons^™

Surveillance And Comparative Genomics Of Bacteria From Hospital And Human Reservoirs, Emily E. Benedict

WUSM Theses and Dissertations – All Programs

Bacteria are diverse and adaptable and, consequently, present in a wide variety of environments. They are capable of growing under intense pressures, including those brought on by the human immune system and disinfection strategies. To survive these pressures, bacteria develop resistances. Antimicrobial resistance, which occurs when a microbe is no longer responsive to the antibiotic intended to control it, is one such adaptation that presents an especially serious threat, as it limits treatment options for infections caused by antimicrobial resistant microbes. Similarly, the ability of bacteria to survive in environments subjected to heavy disinfection efforts, such as intensive care units …

Multiomic And Single-Cell Analysis Of Tumors And Their Immune Microenvironment For Personalized Cancer Therapy, Kartik Singhal

WUSM Theses and Dissertations – All Programs

Precision oncology aims to match cancer treatment to the biology of an individual patient’s tumor. However, tumors that share a diagnosis can differ in their molecular features, cellular composition, clinical course, and response to therapy, making it difficult to determine which treatment will benefit an individual patient. This dissertation integrates genomic, transcriptomic, and single-cell multiomic computational analysis to characterize tumors across their somatic alterations, transcriptional cell states, microenvironment, and the immune response they elicit.

The first study describes a rare case of donor-derived follicular lymphoma following kidney transplantation. Genomic profiling showed that the donor and recipient tumors shared 31 somatic …

Architects Of Mrna Fate: Molecular And Cellular Control Of P-Body Organization In The Drosophilia Melanogaster Female Germline, Samantha Milano

Dissertations, Theses, and Capstone Projects

Processing bodies (P-bodies) are cytoplasmic ribonucleoprotein condensates that regulate mRNA storage, translational repression, and decay. While the biochemical principles governing condensate assembly have been extensively studied in vitro, how P-body organization is established and dynamically regulated in vivo to control specific mRNA populations remains poorly understood. This dissertation investigated the molecular and cellular mechanisms that govern P-body architecture and function in the Drosophila melanogaster female germline. First, I identified the conserved LSm protein Trailer Hitch (Tral) as a central organizer of P-body architecture. Using quantitative confocal and super-resolution microscopy combined with chemical perturbations, I showed that Tral coordinates the …

Effect Of Partial Ablation Of Skeletal Dynamin Related Protein 1 On Mitochondrial Health, Inflammation, And Fibrosis In A Mouse Model Of Duchenne Muscular Dystrophy, Tessa L. Duzz

Graduate Masters Theses

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle weakness, degeneration, fibrosis, and impaired muscle regeneration. Mitochondrial dysfunction is an early pathological feature of DMD and has been linked to excessive mitochondrial fission. Dynamin-related protein 1 (Drp1) is a central regulator of mitochondrial fission, a key process in regulating mitochondrial quality and function. Inhibition of Drp1-mediated mitochondrial fission has shown promise as a potential therapeutic target for alleviating pathology and dysfunction in dystrophic muscle. The objective of this study was to determine whether partial skeletal muscle-specific ablation of Drp1 could improve muscle pathology and mitochondrial health in …

From Genes To Streams: Mitochondrial Approaches To Population Monitoring Of The Santa Ana Sucker Catostomus Santaanae, Mariana Antonio

Electronic Theses, Projects, and Dissertations

This study was developed to use aquatic environmental DNA (eDNA) as a tool to detect the presence of the Santa Ana sucker (Catostomus santaanae), a federally threatened fish species, across the Santa Ana River in Southern California. Environmental DNA is any genetic material that an organism sheds into the environment. We can get an idea of what aquatic species are present when sampling water at a given site. We sequenced the complete mitochondrial genome (mitogenome) of the Santa Ana sucker and designed custom DNA primers to improve eDNA detection accuracy. These primers were selected based on high genetic …

Long-Term Spatiotemporal Change In Coral Reef Fish Populations And Communities In The Philippines, John Christopher Whalen

Biological Sciences Theses & Dissertations

The Visayas Region of the Philippines is a global epicenter of marine fish biodiversity. Hypotheses attribute this peak of species richness within the Coral Triangle to processes that occur at geological time scales. However, changes in biodiversity may occur on ecological time scales, allowing for the assessment of the potential impact of anthropogenic activities. Recent declines in genetic, species, and ecosystem diversity have been observed in the tropics, including the Philippines. Within the Philippines the Visayas Region is considered the epicenter of species adversity due to anthropogenic stressors such as habitat degradation, overfishing, and harvesting individuals for the aquarium trade. …

Computational And Ai Tools For Understanding Telomere-Associated Cancer Mechanisms, Eleni Adam

Computer Science Theses & Dissertations

Telomeres are the protective caps of the human chromosomes and are critical for genome stability. Dysfunctional telomeres caused by their erosion with age and cell proliferation as well as by defects in their maintenance is a major early event leading to genome changes and cancer. Subtelomeres possess the critical role of regulating adjacent telomeres. Due to their complex repeat structure and high variance from one person to another, these areas have not been analyzed in detail. We present a set of computational and machine learning tools to aid in the understanding of subtelomere structure and its rearrangements in cancer.

Initially, …

Towards Improved Stress Resilience, Optimal Growth And Enhanced Biosafety In Transgenic Plants, Xiaotong Chen

All Dissertations

This dissertation investigates biotechnology strategies to improve plant stress resilience, growth, and biosafety in transgenic perennial grasses using creeping bentgrass as a model system. Functional analyses of non-coding RNAs such as miR164 and miR169 showed that regulatory non-coding RNAs influence plant architecture and abiotic stress responses through broad developmental and transcriptional networks, supporting them as valuable engineering targets for complex trait improvement. The dissertation also developed a dual recombinase platform for transgene containment and removal, linking trait engineering with biosafety control. Additionally, the recombinases themselves were examined for their potential impact on heterologous host and were found to reshape plant …

Transcriptional Regulation In The Uterine Luminal Epithelium, Evelyn A. Carrion

Dissertations and Theses (Open Access)

Transcriptional Regulation in the Uterine Luminal Epithelium

Evelyn A. Carrion

Advisor: Richard R. Behringer, PhD

Abstract

The uterus is an organ comprised of multiple tissues that are essential for women’s health and reproduction. The uterus is composed of multiple tissue layers, including the perimetrium, myometrium, and the endometrium. The endometrium is the inner lining of the uterus, and contains the luminal epithelium, glandular epithelium, and stroma. The luminal epithelium is a simple columnar layer of cells that is necessary for embryo implantation. The uterus is derived in part from the embryonic precursor tissue called the Müllerian duct. There are no …

Regulation Of Müllerian Duct Mesenchyme Transcription During Mammalian Sex Differentiation, Haowen Li, Richard R Behringer, Rachel D Mullen

Dissertations and Theses (Open Access)

Sp7/Osterix (Osx) encodes a zinc-finger transcription factor of the Specificity-protein family discovered by Nakashima et al. at the MD Anderson Cancer Center. While primarily recognized for its role in osteogenesis, Osx has also been implicated in mammalian reproductive development, particularly in male sex differentiation, where Müllerian Duct (MD) regression occurs, mediated by anti-Müllerian hormone (AMH) signaling. AMH-induced regression signals are transduced by the mesenchymal tissue surrounding the ductal structure, known as the Müllerian Duct mesenchyme (MDM). It was discovered that AMH signaling is necessary and sufficient for driving Osx expression in MDM. A previous transgenic mouse reporter …

Mutational Analysis Of Domain Functions In The Yeast Decapping Enzyme Dcp2, Jellisa Ewan, Ambro Van Hoof

Dissertations and Theses (Open Access)

In yeast, the major mRNA decay pathway involves deadenylation of the 3’ poly-A tail, followed by decapping of the 5’ m7Gppp cap and subsequent 5’ to 3’ degradation or 3’ to 5’ degradation. This is carried out by Pan2/Pan3 and Ccr4/Not deadenylases, the decapping enzyme Dcp2, and Xrn1 and  RNA exosome exoribonucleases, respectively. The eukaryotic mRNA decapping enzyme complex, Dcp1/Dcp2, is essential in yeast, and deletion of either gene is lethal. However, the deadenylases that act upstream and the 5’ exoribonuclease that act downstream of the decapping step are not, even though they are all highly conserved with no known …

The Impact Of Hypoxia And Androgen Inhibition On Prostate Cancer Cell Dedifferentiation And The Dna Damage Repair Response At Telomeres, Arooba Ayaz

Biomedical Sciences Theses & Dissertations

Long-term Androgen deprivation therapy (ADT) is used to treat Prostate cancer (PCa) but is often met with resistance & the development of Neuroendocrine (NE) PCa which is rarer but more aggressive. Antiandrogens are a part of ADT that work to inhibit androgen receptor in PCa cells. In vitro, PCa cells under long-term antiandrogen treatment become NE-like and adopt stem-like characteristics. The disruption of androgen signaling though the use of antiandrogens impacts many cellular processes that play a major role in cancer cell proliferation such as the DNA damage repair response (DDR) and telomere dysfunction. In vivo, PCa tumors have disorganized …

Epigenetic Regulators Mll3 And Mll4 Sustain Hematopoietic Stem Cell Multipotency, Helen Chenwei Wang

Arts & Sciences Graduate Student Theses and Dissertations

Hematopoietic stem cells (HSCs) maintain lifelong blood production by balancing self-renewal and multilineage differentiation. They are sustained by networks of transcription factors and epigenetic regulators that prime lineage-specific programs while simultaneously preventing activation of any one program up until the moment of lineage commitment. Despite extensive study, it remains unclear how these complex transcriptional programs are coordinated and how specific epigenetic regulators are deployed to reinforce specific cell fate decisions. Epigenetic regulators, MLL3 and MLL4, play a central role in pluripotent embryonic stem cell fate transitions, but their functions in multipotent somatic stem cells are less well characterized. MLL3 (also …

Investigating The Role Of Centromere Deletion In Chromosome Segregation, Azait Imtiaz

ETDs from 2020-2029

Centromeres are critical genomic regions responsible for ensuring accurate chromosome segregation during cell division. Disruptions in the structural or functional integrity of centromeric DNA could impair kinetochore assembly, leading to chromosome missegregation and chromosomal instability (CIN), a hallmark of various human diseases, including systemic sclerosis (SSc). This study investigated the contribution of centromeric DNA damage and deletion to CIN and explored potential pathogenic mechanisms relevant to SSc. We utilized hTERT-immortalized fibroblast cell lines (CHON-002 and BJ-5ta) to implement two complementary approaches: (i) treatment with bleomycin, a chemotherapeutic agent known to induce DNA double-strand breaks (DSBs), and (ii) targeted deletion of …

Elucidating The Function Of Yedk In Response To Dna Damage, Hank Munro

University Honors Theses

Apurinic/Apyrimidinic (AP) sites are one of the most prevalent forms of DNA damage. These lesions arise spontaneously or during base excision repair of modified DNA bases and are potentially mutagenic in both mammalian and bacterial cells. 5-hydroxymethylcytosine binding, ES cell specific (HMCES), a protein found in eukaryotic cells, has been shown to form a stable DNA-protein crosslink with AP sites in single stranded DNA and to reduce the number of AP sites occurring either spontaneously or after alkylative DNA damage, resulting in increased genome stability. YedK, the Escherichia coli ortholog of HMCES exhibits some of the same biochemical properties as …

Polygenic Risk Scores, Sex, And Socioeconomic Factors As Predictors Of Age Of Onset For Major Depressive Disorder, Kaitlyn M. Nowak

USF Tampa Graduate Theses and Dissertations

Major Depressive Disorder (MDD) is a heterogeneous psychiatric condition influenced by genetic, sociodemographic, and environmental factors, yet the extent to which these factors jointly shape the timing of disease onset remains unclear. This study evaluated the effects of polygenic risk scores (PRS), sex, and socioeconomic status (SES) on age of onset for MDD across two independent cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) (N = 486) and the All of Us Research Program (N = 8,014). Analyses were restricted to individuals of European genetic ancestry, and PRS were constructed using both European-ancestry (EA) and multi-ancestry (MA) genome-wide …

The Evolutionary Response Of HawaiʻI ʻAmakihi (Chlorodrepanis Virens) To The Introduction Of Avian Malaria (Plasmodium Relictum), Gabrielle Atkinson

Doctoral Dissertations

The emergence of novel pathogens can impose intense selective pressures on natural populations, driving rapid evolutionary change or precipitating population collapse. In Hawaiʻi, the introduction of avian malaria (Plasmodium relictum) and its mosquito vector (Culex quinquefasciatus) have caused severe declines and extinctions among native forest birds. Yet some populations of Hawaiʻi ʻamakihi (Chlorodrepanis virens) persist across a broad elevational and disease gradient, providing a powerful natural system for examining the genomic basis of rapid adaptation, the role of gene flow in adaptive response, and the potential for parallel evolutionary responses. This dissertation integrates genomic, population genetic, and transcriptomic approaches to …

Marine Heatwaves And Fish Reproduction: Endocrine Responses In The Eurythermal Sheepshead Minnow (Cyprinodon Variegatus), Isabel Villafuerte

Master's Theses

Marine heatwaves associated with climate change are increasing in frequency and severity, posing significant threats to fish populations in shallow habitats such as estuaries and salt marshes. Because temperature is a primary regulator of fish reproduction, understanding how heatwaves affect reproductive physiology is critical for anticipating the biological consequences of ongoing climate change for coastal fishes. Here we examined how simulated heatwave conditions affect the reproductive hypothalamic-pituitary-gonadal (HPG) endocrine axis in the estuarine sheepshead minnow (Cyprinodon variegatus), a eurythermal fish well suited to studying thermal stress responses in estuarine environments. Adult sheepshead minnows acclimated to a daily oscillating …

Quantifying Genetic Diversity In Nematode Feeding Rate, Jacob King

Honors Theses

Understanding how populations persist under changing environmental conditions is a central question in ecology and evolutionary biology. Variation in traits related to resource acquisition may play a key role in determining population survival when resources are limited or fluctuate over time. In this study, I investigated how variation in feeding-related traits influences population persistence using a combination of computational modeling and laboratory experiments. I developed a stochastic, individual-based consumer–resource model to simulate population dynamics across varying levels of trait variance and resource regimes. Across 60,000 simulated populations, increased trait variation consistently reduced extinction risk and extended persistence time, although the …

Morphological And Dietary Consequences Of Hybridization Between Mexican Ducks And Western Gulf Coast Mottled Ducks In A Human-Altered Landscape, Vergie Miranda Musni

Open Access Theses & Dissertations

Hybrid zones provide unique opportunities to study morphological and ecological consequences of hybridization. While landscape genetic studies confirm a newly established contact zone between Mexican Ducks (Anas diazi) and Western Gulf Coast Mottled Ducks (Anas fulvigula maculatus), I provide the first quantitative morphological comparisons of the two taxa and their hybrids in Chapter 1. First, I report significant differences among parental species in lamellar density, body mass, tarsus length, and wing chord lengths, with hybrids exhibiting intermediate or backcross-aligned phenotypes. In contrast, measured bill dimensions did not differ significantly between parental taxa. Despite substantial overlap in bill morphology between Mexican …

Using The Flexon Approach To Rnai For Analysis Of Gene Function In Gonadal Development In C. Elegans, Andrew D. Spalding

Undergraduate Theses

C. elegans, a nematode worm, was used as a model organism to analyze the developmental effects of knocking down the expression of genes that are both essential to worm viability and highly enriched in reproductive tissues. In earlier research, approximately 70 C. elegans genes were identified that are both gonad-enriched and essential. To prioritize which genes should be the focus of future studies, a new strain of C. elegans was produced with three specific genetic variations that: 1) silence essential, somatic gonad-enriched gene expression, 2) limit the effects of this gene silencing to the gonad, and 3) yield a …

Investigating The Taxonomic Uncertainties Of Potentilla Rupincola, Natalie Elizabeth Hieber

Master's Theses

Landscape stewardship is an integral role for land managers that becomes more important when rare or endangered species occur within managed areas. Conservation across the landscape is a primary concern for land managers, but resources allocated for conservation can be limited due to many competing goals. Taxonomic uncertainty surrounding rare and endangered taxa, particularly plant taxa, that have historically been classified solely using morphological features further complicates conservation planning. One such taxon is Potentilla rupincola, a rare plant endemic to the eastern Rocky Mountains in Colorado. For over a century, botanists have debated whether P. rupincola is a distinct species …

Sorghum Grain Secondary Metabolites And Underlying Genetics To Reduce Foodborne Pathogens In Poultry, Maria A. Conti

All Dissertations

The rise in antibiotic-resistant pathogens poses a threat to the poultry industry's ability to maintain animal health, prompting growing interest in alternatives to synthetic antibiotics. The use of non-tannin sorghum [Sorghum bicolor (L.) Moench] in poultry rations offers a valuable alternative, as this cereal grain has a high bioactive profile that can provide health benefits, including antimicrobial (AM) activity. The scope of this study was to examine the AM potential of non-tannin sorghum grain against Clostridium perfringens, a major foodborne pathogen that negatively impacts poultry health and production. To that end, the inhibitory effects of a non-tannin sorghum …

The Genetic Basis Of High Transformation Efficiency In The Model Yeast Saccharomyces Cerevisiae, Mary Kathryn E. Cheek

Biological Sciences Undergraduate Honors Theses

Transformation, a type of horizontal gene transfer, describes the uptake, maintenance, and integration of environmental DNA by cells. Despite the known effects of transformation on evolutionary processes, little is known about the genetic basis of this phenomenon. Saccharomyces cerevisiae is a eukaryote able to transform at quantifiable rates when made chemically competent and treated with a heat shock. S. cerevisiae also has variation in transformation efficiencies between various strains, and high recombination rates allow for sufficient allele “shuffling” in intercross populations. This project utilizes a bulk segregant analysis approach to compare sequencing data between transformant pools and non-transformant pools of …

Precursor Rna Properties Driving Cryptic 3’ Splice Site Selection In Sf3b1 Mutant Malignancies, Austin A. Herbert

All Dissertations

SF3B1 is a core component of the spliceosome involved in branch point recognition and 3’ splice site selection. SF3B1 is commonly mutated in myelodysplastic syndromes and other blood cancers with the K700E mutation being the most frequent. This mutation of SF3B1 induces cryptic 3’ splice site activation in hundreds of genes. Introduction of such cryptic 3’ splice sites can shift the reading frame of protein coding transcripts, causing the transcript to be tagged for nonsense-mediated decay or resulting in the production of a truncated protein. Both these scenarios can lead to down-regulated protein expression. Sequence and structural properties of precursor …

Genetic Screen For Regulators Of Pol4, A Dna Repair Polymerase In Saccharomyces Cerevisiae, Pasang Dolma Sherpa

Theses and Dissertations

In Saccharomyces cerevisiae, DNA polymerase 4 (POL4) is the beta repair polymerase, the product of the POL4 gene, and is involved in base excision repair (BER) and microhomology-mediated end joining (MMEJ). Despite its involvement in these repair pathways and its conservation across eukaryotes, deletion of POL4 shows no detectable phenotype under standard laboratory conditions. I hypothesized that unknown genes act as backup systems, providing redundant activities that allow pol4Δ cells to survive. To test this, a genetic screen for mutants showing synthetic lethality with pol4Δ was implemented. I constructed a strain lacking the POL4 gene and carrying …

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Dissecting The Complex Genomic Landscape Underlying Oxidative Stress Resistance Using Natural Variation In Yeast, Sonali Lakshika Anne Lenaduwe

Graduate Theses and Dissertations

Stress is experienced across the tree of life. Survival in fluctuating environments depends on a robust genetic architecture. This dissertation examines the genetic and metabolic determinants underlying one such adaptive response: cross-protection. Leveraging natural variation in the stress responses of budding yeast, Saccharomyces cerevisiae, I examine the genetic variation contributing to ethanol-induced cross-protection against oxidative stress. Acquired stress resistance, in which mild pre-exposure improves survival to subsequent stresses, is prevalent across diverse organisms and can involve both same-stress and cross-protection. Using high-throughput bulk segregant analysis (BSA-seq) and advanced intercross mapping populations derived from natural yeast isolates, I identify quantitative trait …

Using The Flexon Approach To Rnai To Identify Essential Genes That Affect Gonadal Development In C. Elegans, Joyce S. Lefevers

Undergraduate Theses

To elucidate the molecular role of essential genes in the gonadal development of Caenorhabditis elegans (C. elegans) it is necessary to utilize specialized molecular techniques such that the phenotypic effects of gene knockdown can be studied while the viability of the organism is preserved. Shaffer and Greenwald (2022) developed the floxed exon (flexon), a tool that improves upon previous approaches to spatiotemporal control of gene expression. The flexon subunit is made up of an artificial exon with a stop cassette flanked by artificial introns which, when inserted into a gene of interest, prevents the expression of that gene. …

From Bench To Bedside: Unraveling The Role Of Sarm1 In Chronic Human Neurodegenerative Disease, Caitlin Dingwall

Arts & Sciences Graduate Student Theses and Dissertations

Axon degeneration (AxD) is an early and often causative event in many neurodegenerative diseases, yet no treatments exist to halt the breakdown of axons. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. NMNAT2 is a highly labile protein produced in the soma and trafficked into the axon. Nerve injury blocks axonal transport and leads to rapid depletion of axonal NMNAT2, causing NMN buildup and NAD+ loss. Recent breakthroughs led to the discovery that SARM1 is activated by an increase in the NMN to NAD+ ratio. While the SARM1 axon degeneration pathway …