Genetics and Genomics Commons^™

Intracellular Survival Of Staphylococcus Aureus In Macrophages During Osteomyelitis, William A. Lathram, Christopher D. Radka

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies – including biofilm formation, small colony variants, and inhibition of phagolysosomal killing – further enhance persistence and immune evasion. While these …

Temporal Dynamics Of Programmed Genome Rearrangement In Sea Lamprey Embryogenesis: A Deep Learning & Lightsheet Imaging Approach To Studying Early Developmental Transitions, Kasturi Rajandran

Theses and Dissertations--Biology

Programmed genome rearrangement (PGR) in the sea lamprey (Petromyzon marinus) leads to the elimination of ~0.5Gb (20%) of the germline genome during early embryogenesis, yet its timing relative to the maternal-to-zygotic transition (MZT) remains unclear. In this study, we imaged embryos cleared at 3-hour intervals (up to 72 hours post fertilization (hpf)) using high-resolution lightsheet fluorescence microscopy and a custom deep-learning image-analysis pipeline (~80% accuracy) to quantify nuclei and micronuclei counts. Micronuclei, which are the hallmarks of PGR first appear between 24 to 27hpf (vs ~36hpf previously reported) indicating PGR starts earlier than previously reported in the sea …

Revolutionizing Grapevine Breeding Programs: A Mobile Genome Editing System For Perennial Crops, Bridget Bolt

Theses and Dissertations--Plant and Soil Sciences

Grapevine (Vitis vinifera) faces unprecedented challenges from climate change, with up to 90% of current growing regions potentially becoming unsuitable for production within decades. Traditional breeding approaches require 25-30 years for variety development, creating a time constraint incompatible with the pace of environmental change. This research establishes the approach for a novel mobile RNA-based gene editing platform that addresses longstanding bottlenecks in grapevine improvement while preserving cultivar identity and reducing breeding timelines.

This research developed a three-component system for transgene-free gene editing in grapevine. First, a mobile CRISPR/Cas9 system was established using Agrobacterium rhizogenes transformation and the cut-and-dip …

Accurate Body Weight Class Prediction From Mirna And Gene Expression In Blood And Saliva Samples, Kimberly Lettner

Master of Science in Forensic Science Directed Research Projects

miRNA interference on protein abundance related to glucose uptake and lipid production has been evaluated in biomedical research and linked to metabolic disorders like severe obesity. The direct regulation of protein abundance caused by miRNAs on a person’s metabolism can lead to an increased weight and overall size. Body size, measured by BMI, provides additional physical descriptions that can be combined with hair color, eye color, age, and skin pigment to aid investigations of unidentified remains or unknown suspects not found in a database. The purpose of this project was to evaluate the miRNA expression of target biomarkers in dried …

Investigating Mitochondrial Stress Response Mechanisms In Aging, Aileigh E. Daniel

Theses and Dissertations

Mitochondrial dysfunction is widely recognized as a key contributor to aging and age-related diseases. The concept of mitohormesis suggests that low levels of ROS can activate stress-responsive transcription factors, promoting adaptive mechanisms that enhance longevity. We hypothesized that changes in protein abundance under conditions of mild mitochondrial stress reflect an adaptive response, and that commonly altered proteins across diverse genetic backgrounds of mitochondrial stress can help identify key regulators of stress resilience and aging. Our study identified conserved mitochondrial stress response pathways and highlighted candidate regulators for further investigation. These regulators appear to impair mitochondrial energy production by downregulating ATP …

Identification Of Benzothiophene-Derived Inhibitors Of Flaviviruses By Targeting Rna-Dependent Rna Polymerase, Leah Liu Wang, Shazeed-Ul Karim, Aidan Hand, Ryan Brunkhorst, Mackenna Petersen, Sarah Altam, Yi Liu, Luwen Zhang, Fengwei Bai, Shi-Hua Xiang

School of Biological Sciences: Faculty Publications

Flaviviruses such as Dengue, West Nile, and Zika viruses are mosquito-borne RNA viruses that can cause serious diseases in humans. To develop effective drugs for treating these viruses’ infections, we create a new approach for developing common or shared drugs that may work for several different viral species of flaviviruses. It is based on the conserved RNA-dependent RNA polymerase (RdRp), which is the key enzyme for viral replication. We built up a common structure of RdRps (POLcon) from their consensus sequence. A conserved Triple-D structural motif was identified at the active site of POLcon that has been used for virtual …

Presence Of The Ade Multidrug Systems And Response To Triclosan Exposure In Acinetobacter Baumannii From Animal Origins, Sirawit Pagdepanichkit, Rungtip Chuanchuen

The Thai Journal of Veterinary Medicine

Thirty Acinetobacter baumannii from animal origins were obtained from 210 animal carcasses submitted for post-mortem examination, including dogs (n=112), cats (n=45), rabbits (n=17), birds (n=15), pigs (n=7) and exotic animals (n=14). All the isolates were evaluated for antimicrobial susceptibility with absence and presence of efflux inhibitors i.e. reserpine and carbonyl cyanide m-chlorophenylhydrazone (CCCP) and expression profile of important six multidrug efflux systems (i.e. AdeABC, AdeDE, AdeFGH, AdeIJK, AbeM and AmvA). Fifteen isolates expressing different Ade multidrug efflux pumps were selected for determining transcription levels and regulatory mutations. A continuous in vitro exposure experiment with benzalkonium chloride, chlorhexidine and triclosan …

Next Generation Sequencing Based Profiling Of Genes In Patients With Syndromic Forms Of Retinitis Pigmentosa, Harshavardhini G

Theses and Dissertations

India is one of the largest populations in the world and is estimated to have a high prevalence of Retinitis Pigmentosa (RP). RP is clinically and genetically heterogenous, characterized initially as night blindness, leading to complete vision loss due to retinal degeneration. RP can occur in non-syndromic or syndromic forms, affecting other organs as observed in Bardet Biedl Syndrome (BBS) and Usher syndrome (USH).

BBS is characterized by RP, polydactyly, obesity, renal anomalies and learning difficulties. USH is characterized by RP and sensorineural hearing loss (SNHL), with variable presence of vestibular dysfunction. Nextgeneration sequencing (NGS) has become a cost-effective technology …

Gonadal Absence Of Pig-1: Exploration Of Pig-1 In The Gonad Of Caenorhabditis Elegans, Winston S. Bennah

Undergraduate Theses

Caenorhabditis elegans are model organisms frequently studied to better understand biological processes. They have short life spans and produce a large number of progeny. Additionally, many of their molecular development processes can be found in human, providing insight into cell death and cell fate. In this project, our research aims to create a triple mutant strain to test the importance of the pig-1 gene in the gonad of C. elegans. This strain carries the following alleles: ckb-3::degron; him-8; gfp::pig-1. The pig-1 gene has been previously studied in neuroblast cells in C. elegans and is required for …

Single-Molecule Studies Reveal The Off-Pathway Early Paused State Intermediates As A Target Of Streptolydigin Inhibition Of Rna Polymerase And Its Dramatic Enhancement By Gre Factors, Anatolii Arseniev, Mikhail Panfilov, Georgii Pobegalov, Alina Potyseva, Polina Pavlinova, Maria Yakunina, Jookyung Lee, Sergei Borukhov, Konstantin Severinov, Mikhail Khodorkovskii

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Antibiotic streptolydigin (Stl) inhibits bacterial transcription by blocking the trigger loop folding in the active center of RNA polymerase (RNAP), which is essential for catalysis. We use acoustic force spectroscopy to characterize the dynamics of transcription elongation in ternary elongation complexes (ECs) of RNAP in the presence of Stl at a single-molecule level. We found that Stl induces long-lived stochastic pauses while the instantaneous velocity of transcription between the pauses is unaffected. Stl enhances the short-lived pauses associated with an off-pathway early paused state intermediates of the RNAP nucleotide addition cycle. Unexpectedly, we found that transcript cleavage factors GreA and …

Characterizing Mechanisms Of Dna Repair And Genome Stability, Joshua Turner

All Dissertations

Every day our cells are bombarded with DNA lesions that threaten the stability of our genome. To help maintain genomic integrity our cells evolved to have a network of enzymes dedicated to repairing DNA lesions. Upon encountering a site of DNA damage, a cell recruits enzymes that remodel the stalled replication fork by reannealing the newly synthesized DNA together known as fork regression. Loss of fork regression activity has been shown to promote replication stress resistance after induced DNA damage. In this thesis, I discuss the role F-Box Helicase 1 (FBH1) plays in fork regression and how FBH1 promotes the …

The Role Of Siamese In G2 Checkpoint Regulation In Arabidopsis Thaliana, Martha A. Schwall

LSU Doctoral Dissertations

Cyclin-cyclin dependent kinase (Cyclin-CDK) pairs regulate progression through the checkpoints of the cell cycle. They bind with some specificity and must be bound to for their regulative properties to be active. The presence of cyclin-CDKs is conserved throughout eukaryotes, while differences in specifics exist between yeast, animals, and plants. In Arabidopsis, SIAMESE (SIM) is a CDK inhibitor that restricts progression through mitosis. Overexpression of SIM is required for endoreplication in Arabidopsis trichomes, and overexpression of SIM results in increased endoreplication in leaf epidermal cells. SIM is expressed at high levels in the root elongation zone, where it plays a …

Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to …

Monitoring The Seasonal Presence Of The Blue Shiner, Cyprinella Caerulea, In Little River Canyon National Preserve Using Environmental Dna, Deanna Meadows

Theses

The study of environmental DNA (eDNA) has provided researchers with a more accessible and sensitive way to identify the presence of specific species compared to traditional monitoring methods. eDNA enables species detection by analyzing environmental samples such as water or soil, which contain genetic material shed by organisms in a given area. Research indicates that eDNA techniques have become a valuable method for monitoring threatened and invasive species, proving particularly reliable for detecting aquatic species compared to traditional techniques. Quantitative PCR (qPCR) has been used in numerous eDNA studies, as it provides for greater accuracy than conventional PCR. Cyprinella …

Effects Of Microplastic Biofilms On An Anthropogenically Impacted Suburban Lake, Paris M. Velasquez

Masters Theses

Plastics have been observed in every location on the planet, and their prevalence in the environment is due in part to their strong resistance to degradation. Inland lakes are susceptible to plastic pollution by highway runoff, which contains plastic fragments of brake pads, car tires, litter, and road paint. These plastics eventually enter freshwater environments and degrade into microplastics (

Antarctic Glacier Melting Modeling Distribution Of Bacterial Community Structure, Corina Itcus, Constantin Marin, Soon Gyu Hong, Manuela Elisabeta Sidoroff, Cristian Coman, Cristina Purcarea

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Elevating Microrna Levels By Targeting Biogenesis With Steric-Blocking Antisense Oligonucleotides, Mallory A. Havens, Anthony J. Hinrich, Frank Rigo, Michelle L. Hastings

Biology Department Faculty Articles

MicroRNAs (miRNAs) are regulators of gene expression, and their dysregulation is linked to cancer and other diseases, making them important therapeutic targets. Several strategies for targeting and modulating miRNA activity are being explored. For example, steric-blocking antisense oligonucleotides (ASOs) can reduce miRNA activity by either blocking binding sites on specific mRNAs or base-pairing to the miRNA itself to prevent its interaction with the target mRNAs. ASOs have been less explored as a tool to elevate miRNA levels, which could also be beneficial for treating disease. In this study, using the PKD1/miR-1225 gene locus as an example, where miR-1225 is located …

Project Give: Using A Virtual Genetics Service Platform To Reduce Health Inequities And Improve Access To Genomic Care In An Underserved Region Of Texas, Blake Vuocolo, Roberta Sierra, Daniel Brooks, Christopher Holder, Lauren Urbanski, Keila Rodriguez, Jose David Gamez, Surya Narayan Mulukutla, Ana Hernandez, Alberto Allegre, Humberto Hidalgo, Sarah Rodriguez, Sandy Magallan, Jeremy Gibson, Juan Carlos Bernini, Melanie Watson, Robert Nelson, Lizbeth Mellin-Sanchez, Nancy Garcia, Lori Berry, Hongzheng Dai, Claudia Soler-Alfonso, Kent Carter, Brendan Lee, Seema R Lalani

Faculty, Staff and Students Publications

BACKGROUND: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services. Funded by the National Center for Advancing Translational Sciences, Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to reduce the time to diagnosis and increase provider knowledge of genomics in this region, with the goal of …

Characterizing Border Associated Macrophages During Spinal Cord Regeneration, Addison Vogt, Dana Shaw, Mayssa Mokalled

Undergraduate Research Symposium

The human central nervous system has limited regenerative ability, with injuries to the spinal cord (SC) often resulting in paralysis. Alternatively, zebrafish have enhanced innate regenerative capacity and regain full motor function following spinal cord injury (SCI). Immune activation following SCI is necessary to provide a permissive environment for tissue repair, but the immune pathways necessary for SC regeneration are not well characterized. In previous data, we have found that while immune activation is persistent into the chronic phases of SCI response in mammals, zebrafish achieve full immune clearance within 48 days post SCI. We hypothesize that one key distinction …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

The Seat Of Singular Gene Choice: Dissecting The Role Of Odorant Receptor Enhancer Elements That Lead To Mammalian Olfactory System Expression, Alessandro M. Rosa

Dissertations, Theses, and Capstone Projects

Odorant receptors (ORs) were first identified in 1991 and the initial data strongly suggested that ORs were part of a large superfamily of G-protein-coupled receptors. Within a few years of the discovery of the OR superfamily, it became clear that each OR allele was exclusively expressed in olfactory sensory neurons (OSN), and that this singular expression leads to cellular identity. Many studies over the past thirty years have sought to unlock the mysteries of the mechanism for monoallelic and monogenic OR gene activation and expression in OSNs, however no definitive model for singular gene expression has emerged.

Using a series …

From Turf To Turf: Fungal Invasion Of Ascocoryne Turficola In A Northern Michigan Bog, Evan L. Coscarelli-Trott

All NMU Master's Theses

This is the first paper to report Ascocoryne turficola Boud. 1905 (Helotiales: Ascomycota) within the United States. It is an obligate bog fungus native to Europe and Siberia, where it is extremely rare across most of its range. A. turficola appeared at Lily Pond Bog in Marquette, Michigan (87.47º W, 46.59º N) in 2019, almost contemporaneous with anecdotal reports in Minnesota and Ontario. Since 2019, the Lily Pond population has exploded and become the dominant fungus in this bog but has yet to spread to similar bogs nearby. This species is adapted to long distance dispersal and carries the potential …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Molecular Characterization Of Viral Escape From Art And Crispr Hiv-1 Excision In Infected Humanized Mice, Chen Zhang

Theses & Dissertations

Not available.

Uncovering The Hidden Diversity Of Antibody Heavy Chains And Their Implications For Autoantibody Mediated Disease., Easton Earl Ford

Electronic Theses and Dissertations

Understanding the diversity of antibody (IG) molecules at the DNA and RNA level is imperative for understanding immunological processes and disease. Much of the work to uncover IG diversity has been focused on diversity in the variable region of the IG molecule which is crucial for antigen binding. However, the diversity of the constant region responsible for the functions of IG has largely been ignored in the field of immunogenetics. The work presented in this thesis challenges the dogma that the constant region is invariant in terms of genetic diversity. In this thesis we present the development of a long-read …

Industrial Applications Of Molecular Techniques., Jesse Lee Rozsa

Electronic Theses and Dissertations

Multidisciplinary research is vital in modern science. Combining molecular genetics with engineering disciplines such as material science, robotics, or 3D printing is not a new concept but one that can continue to lead to breakthroughs that will benefit society. Science does not and should not occur in a vacuum, and, in early 2020, the world saw the emergence of a pandemic that shifted the focus of scientific research for a time. This manuscript describes aspects of this journey and the fruit that was born from this historic event. In this dissertation, we used plants and bacteria to produce compounds that …

Regulation Of Serpina1 Mrna Expression By Environmental Conditions In Hepatocyte Cells, Fnu Jiamutai

All Theses

The SERPINA1 gene encodes the critical protease inhibitor α-1-antitrypsin (A1AT). A1AT represses neutrophil elastase activity to protect lung tissue from inflammatory damage. A deficiency in α-1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD). Pathogenic genetic variants in SERPINA1 are also associated with A1AT protein misfolding and liver cirrhosis. The regulatory mechanisms of SERPINA1 expression are not well understood, but previous studies suggest that alternative polyadenylation in the 3' untranslated region (3'UTR) affects A1AT protein expression. In this study, we used the liver cancer cell line HepG2 to determine how environmental conditions influence SERPINA1 mRNA expression and post-transcriptional regulation. We …

Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …