Genomics Commons^™

Effects Of M6a Dna Methylation By Bacterial Methyltransferase In Colorectal Cancer, Fabian Alejandro Mendoza Galvan

Dissertations and Theses (Open Access)

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous …

Characterization And Advancement Of Molluscan Venom Gland Cell Model Systems, James V. Parziale

Dissertations, Theses, and Capstone Projects

Venomous mollusks, including cone snails and coleoid cephalopods, produce rich repertoires of bioactive peptides with profound effects on cellular physiology, yet there are few tractable experimental systems that exist to study their development, maintenance, and venom secretion. Although therapeutics such as the cone snail peptide Ziconotide demonstrate the biomedical potential of molluscan venoms, progress in understanding how venom glands form, function, and evolve has been hindered by the lack of reliable husbandry and the complete absence of in vitro cell models. Modern comparative genomics has revealed widespread convergent evolution across venomous lineages, but molluscan datasets remain underrepresented, limiting insights into …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Epigenetic Modifications In Dedifferentiated Liver Cells To Restore Lost Liver Function, Shreya Sharma

Masters Theses

The goal of the study is to investigate whether the epigenetic modifications can enhance the restoration of liver gene expression in dedifferentiated hepatoma cells or not. For the study, we used dedifferentiated H11 hepatoma cell lines which overexpress one of a panel of introduced candidate liver-enriched transcription factors H11-HNF1a, H11-CREB3L3, H11-CREG1, H11- HHEX, H11-HNF6, and H11-IGFBP1. The cells were treated with the DNA methyltransferase inhibitor 5-azacytidine and the histone deacetylase inhibitor sodium butyrate, both individually and in combination. Gene expression analysis was determined by RT-qPCR, which revealed that while transcription factor overexpression alone produced limited activation, epigenetic modulation, particularly Histone …

Retinal Precursor Cell Enriched Multiomic And Pseudo-Time Analysis Of Developing And Reprogrammed Photoreceptors, Brendon M. Patierno

Dissertations, Theses, and Capstone Projects

The vertebrate retina is a complex tissue made up of seven major cell subtypes which during development must differentiate and localize into a highly organized structure. These neuronal cells do not regenerate if damaged or diseased, and the progressive deterioration of cone photoreceptor cells is the leading cause of age related blindness. Currently there are no cures for this disease, but one promising therapeutic avenue is cell transplantation research. If we can further elucidate the gene regulatory networks that define cone cell development, this knowledge could be applied to the generation of healthy cone cells in clinically relevant models.

The …

A Toi Rna Editing In Three Members Of The Microbotryum Violaceum Fungal Complext And Characterization Of Adar Genes Of Microbotryum Superbum., Shikhi Baruri

Electronic Theses and Dissertations

A-to-I RNA editing is a process that occurs post-transcriptionally. Through this process, adenosine (A) is replaced by inosine (I) in RNAs by adenosine deaminase enzymes that act on the single-stranded RNA. These enzymes, also known as ADARs, act on RNA. The translation and splicing mechanisms subsequently interpret inosine as guanosine (G), which effectively alters genetic information. This kind of RNA alteration can cause both nonsynonymous and synonymous changes in codon, which may have an impact on protein function. A group of over 89 basidiomycete fungal species known as the Microbotryum violaceum complex infects a similarly large group of plant host …

Metabolic And Physiological Regulation In C. Elegans: Insights Into Sperm Activation And Peroxisome-Mediated Longevity, Yash Flora

LSU Doctoral Dissertations

Organelle dynamics lie at the heart of cellular signaling and metabolic regulation, orchestrating physiological processes such as reproduction and aging across the lifespan. In this dissertation, I investigate how organelle-based signaling coordinates sperm activation and modulates organismal aging in the nematode Caenorhabditis elegans. I identify SPIN-4, a previously uncharacterized Spinster family transporter, as a key regulator of spermiogenesis. SPIN-4 is strongly expressed in developing sperm, localizes to the plasma membrane, and promotes sperm activation by facilitating the export of sphingosine-1-phosphate (S1P). Loss of spin-4 results in defective pseudopod formation, reduced motility, and compromised fertility, phenotypes that can be rescued …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Genetic Analysis Of Methionine Restriction-Associated Mitochondrial Unfolded Protein Response Signaling., Josh D. Dodge

Biology Dissertations - Archive

The lifespan of an organism is dictated by various genetic and environmental factors. One such determinant is the health of mitochondria which are organelles that mediate various critical cell functions including a significant role in generating the vast supply of cellular energy. Indeed, the gradual decline of mitochondrial function is believed to be a hallmark and possible cause of aging. Paradoxically, mild mitochondrial dysfunction early in life extends lifespan in various model organisms. Cells use diverse approaches to promote mitochondrial homeostasis, including the transcriptional reprogramming of cells by mitochondrial unfolded protein response (UPRmt) to mitigate mitochondrial stress. Consistently, UPRmt activation …

Testing Vivo-Morpholino Mediated Gene Knockdown Of Stat6, Spi1b, And Hnf4Α In Adult Threespine Stickleback, Stella Dipippo

Honors Scholar Theses

The fibrotic immune response to the cestode parasite, Schistocephalus solidus, varies among threespine stickleback populations. Fibrosis suppresses parasite growth but has costly effects on the fish. Previous genomic studies in stickleback have suggested potential roles of Spi1b, STAT6, and HNF4α in modulating fibrosis severity, but there is presently no evidence for this in-vivo. We used antisense vivo-morpholino oligonucleotides (MOs) to attempt to knockdown the expression of each gene in the liver, spleen, and intestine of adult stickleback. Vivo-MOs have been proven effective in other species of teleost fish, as well as in mice and humans, but …

Big Life-Science: Study Of Omics From Microscopic To Mesoscopic Scales, Jiarui Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

The human genome project at the turn of the century opened a new era of life science research and formed various omics characterized by holistic high-throughput research. The initial omics research was mainly carried out at the molecular level, such as genomics, transcriptomics, proteomics, etc., showing a new paradigm of data-driven research. With the development of research technologies, the omics research has risen to the mesoscopic level, the representative is the “Human Cell Atlas” project launched in 2017. At present, researchers have been able to carry out omics research at the level of tissues, organs, and even individuals, and resulted …

Promoting Ecosystem Based Marine Management Through A Marine Ecological Classification And Zoning System, Wenhai Lu, Xiao Li, Meng Cui

Bulletin of Chinese Academy of Sciences (Chinese Version)

Ecosystem based ocean management is an important means of building marine ecological civilization. The current marine ecological classification and zoning in China comprehensively sorts out the types and natural geographical characteristics of marine ecosystems, divided the Chinese seas and adjacent waters into several levels of ecological spatial units according to different scales, effectively characterizes the geographical distribution features of marine biological communities and their habitats, and provides effective support for ecosystem based marine management. This study analyzed the practical significance of marine ecological classification and zoning. Based on a review of the development of marine ecological classification and zoning, this …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …

Research On Innovative Development Path And Policy Guarantee Of China’S Synthetic Biology Industry, Hongjun Geng, Chang Wang

Bulletin of Chinese Academy of Sciences (Chinese Version)

Synthetic biology is hailed as the third revolution in life sciences after the discovery of the DNA double helix structure and genomic technology, and is the core driving force for the leapfrog development of next-generation biomanufacturing and the future bioeconomy, opening up an opportunity window for the reshaping of the global manufacturing map. How to strategically position the synthesis biology industry and seize the strategic high ground in the industry is a core topic of interest for global science and technology powers and manufacturing powers. Based on the identification of problems in the development of China’s synthesis biology industry, this …

Recent Progress And Perspectives On Development Of Gene Editing Tools, Zixian Liu, Chengping Li, Gogo Jun-Jie Liu

Bulletin of Chinese Academy of Sciences (Chinese Version)

The gene editing field has witnessed remarkable advancements in recent years, leading to the establishment and refinement of multidimensional gene editing platforms. These innovations have enabled precise targeted gene knockout, repair, and insertion. These tools have stimulated significant progress in fundamental research, therapeutics, agriculture, environment protection, and industrial applications. In this review, we provide a comprehensive overview of the milestones in gene editing tool development and offer perspectives on potential future directions for this rapidly evolving field.

Corals In Crisis: A Transcriptomic Investigation Of Stony Coral Tissue Loss Disease, Kelsey M. Beavers

Biology Dissertations - Archive

Coral reefs face existential threats due to climate change and human activities. The combined effects of ocean warming, overfishing, pollution, and habitat destruction have fundamentally altered the functionality of coral reefs and are driving a drastic increase in the prevalence and severity of coral disease outbreaks. Stony coral tissue loss disease (SCTLD) has emerged one of the most devastating disturbances to Caribbean reef ecosystems on record. Despite notable progress, the cellular mechanisms driving SCTLD pathogenesis remain poorly understood. To address this issue, my dissertation investigates the gene expression, histopathology, immune protein activity, and symbiont community dynamics involved in SCTLD progression …

Functional Analyses Of The Polycomb-Group Genes In Sea Lamprey Embryos Undergoing Programmed Dna Loss, Cody Saraceno

Theses and Dissertations--Biology

During early embryonic development, the sea lamprey (Petromyzon marinus) undergoes programmatic elimination of DNA from somatic progenitor cells in a process termed programmed genome rearrangement (PGR). Eliminated DNA eventually becomes condensed into micronuclei, which are then physically degraded and permanently lost from the cell. Previous studies indicated that many of the genes eliminated during PGR have mammalian homologs that are bound by polycomb repressive complex (PRC) in embryonic stem cells. To test whether PRC components play a role in the faithful elimination of germline-specific sequences, we used a combination of CRISPR/Cas9 and lightsheet microscopy to investigate the impact …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Structural Diversity And Stress Regulation Of The Plant Immunity-Associated Calmodulin-Binding Protein 60 (Cbp60) Family Of Transcription Factors In Solanum Lycopersicum (Tomato), Vanessa Shivnauth, Sonya Pretheepkumar, Eric J. R. Marchetta, Christina A. M. Rossi, Keaun Amani, Christian Castroverde

Biology Faculty Publications

Cellular signaling generates calcium (Ca2+) ions, which are ubiquitous secondary messengers decoded by calcium-dependent protein kinases, calcineurins, calreticulin, calmodulins (CAMs), and CAM-binding proteins. Previous studies in the model plant Arabidopsis thaliana have shown the critical roles of the CAM-BINDING PROTEIN 60 (CBP60) protein family in plant growth, stress responses, and immunity. Certain CBP60 factors can regulate plant immune responses, like pattern-triggered immunity, effector-triggered immunity, and synthesis of major plant immune-activating metabolites salicylic acid (SA) and N-hydroxypipecolic acid (NHP). Although homologous CBP60 sequences have been identified in the plant kingdom, their function and regulation in most species remain unclear. In …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

Neonatal Islet-1+ Cardiovascular Progenitor Cell-Derived Exosomes And Their Functional Ability To Regulate Proliferation, Lourdes Ceja

Electronic Theses, Projects, and Dissertations

Heart failure affects many people around the world and can lead to disease progression and death. Consequently, new stem and exosome-based therapies are needed to address this major health issue and to provide therapeutic options that will improve outcomes for the increasing number of patients with heart disease. Stem cell-derived exosomes have captivated researchers’ attention over the past couple of years based on their functional role in cellular signaling which highlights the vital component of the secretome of stem and progenitor cells. Since neonates have significantly enhanced regenerative ability, we hypothesized that exosomes isolated from Islet-1+ expressing neonatal human cardiovascular …

Noxious Cellular Injury Triggers An Oxidative Stress Gene Response, Shawyun Khoshneviszadeh

Master of Science in Integrative Biology Theses

Wound and regeneration involves a series of complex processes that can induce oxidative stress by elevating intracellular reactive oxygen species (ROS) levels. In this study, we used RNA-seq and qPCR to examine the molecular signature of Human Embryonic Kidney cells (HEK-293T) stimulated with Crotalus atrox (CA) venom. NGS data was assembled and annotated utilizing the Illumina paired-end RNA-seq approach with software packages HISAT2 and StringTie. Results showed 243 genes were differentially expressed (106 upregulated, 137 downregulated) between CA venom stimulated and non-stimulated cells (p<0.05). HEK-293T stimulated with CA venom for 4 hours showed an increase in the expression of oxidative stress response genes (e.g., TOMM6, EGR (1,2,3), HSP70 (1A, 1B), SPRY4, ETV5, and EMP1) (Fold-Change (fc) >2.0). Significantly downregulated genes were associated with many novel transcripts/proteins such as AC117378, AD000671, and AC023509. …

Development Of Cloning Vehicles For Expression Of Gc-Maf In Yeast, Tammy Tran, Seohyun Lee, Jane Yu, Wilson Wu

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Spr-5; Met-2 Maternal Reprogramming Cooperates With The Dream Complex To Regulate Developmental Cell Fates, Jazmin Dozier, Sandra Nguyen, Brandon Carpenter

Symposium of Student Scholars

Histone methylation is a post-transcriptional modification to the N-terminal tails of histone core proteins that regulates DNA accessibility, and consequently, gene expression. Like DNA, histone methylation can be inherited between generations, and is highly regulated during embryonic development. At fertilization, histone methylation must undergo maternal reprogramming to reset the epigenetic landscape in the new zygote. During maternal reprogramming of histone methylation in the nematode, C. elegans, H3K4me (a modification associated with active transcription) is removed by the H3K4 demethylase, SPR-5, and H3K9me (a modification associated with transcriptional repression) is subsequently added by the histone methyltransferase, MET-2. Recently, it was …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Human 5’-Tailed Mirtrons Are Processed By Rnasep, Mohammad Farid Zia

Dissertations

Approximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed is …

Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina

Biology Faculty Publications

Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …