Molecular Genetics Commons^™

Exploring The Role Of Transcription Factor Nrf1 In Autophagy And Inhibiting The Nrf1 Bounce-Back Response, Madison A. Ward

Theses and Dissertations

Cells exposed to proteotoxic stress invoke adaptive responses aimed at restoring proteostasis. Our previous studies have established a firm role for the transcription factor Nuclear factor-erythroid derived-2-related factor-1 (Nrf1) in responding to proteotoxic stress elicited by inhibition of cellular proteasome. Following proteasome inhibition, Nrf1 mediates the synthesis of new proteasomes, thus enabling cells to mitigate proteotoxic stress. Here, we report that under similar circumstances, multiple components of the autophagy-lysosomal pathway (ALP) were transcriptionally upregulated in an Nrf1-dependent fashion, thus providing the cells with an additional route to cope with proteasome insufficiency. In response to proteasome inhibitors, Nrf1-deficient cells exhibited profound …

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 …

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 …

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 …

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 …