Molecular Genetics Commons^™

An Investigation Of Entamoeba Histolytica Chitin Synthases And Other Encystation Factors In Early Encystation, John N. Talledo

All Theses

Entamoeba histolytica is a food-and-water-borne human protozoan pathogen that relies on a two-stage life cycle for successful proliferation outside of the host. E. histolytica exists in its dormant cyst form while outside of its host and converts to the motile trophozoite (amoeba) form in the small intestine. The trophozoites colonize the large intestine to cause symptomatic disease in ~10% of infections, resulting in ~100 million cases of amoebic dysentery each year. Trophozoites can convert back to the cyst form, which is shed in feces to continue the infection cycle.

Currently, there is a lack of understanding of the exact molecular …

Characterizing The Molecular Response Of Embryonic Zebra Finch To Acute Sound Playback, Saidat O. Adeniran-Obey Miss

All Theses

Auditory stimuli are important cues that influence developmental plasticity in animals and are important for development and adaptation to an ever-changing environment. In the zebra finch (Taeniopygia guttata), there is evidence of adaptive developmental reprogramming in response to a prenatal ‘heat call’. Embryos exposed to this heat call exhibit changes in growth rate post-hatch, increased heat resistance, and enhanced reproductive success at maturity. However, it has long been assumed that embryonic zebra finches cannot respond to sound due to the immaturity of their auditory system. These findings raise the critical question of whether late-stage zebra finch embryos can, …

Purple Tomatoes Boost Nutrition Crop Value And Create New Opportunities For United States (U.S) Agriculture, Tariq Alam

Agronomic Crops

The agricultural landscape in the United States is continually evolving, with growers and the tomato industry seeking innovative ways to meet consumer demands while enhancing profitability. The introduction of both bioengineered and classically bred anthocyanins-enriched purple tomatoes presents a unique opportunity for U.S. growers to cultivate a high-value crop that appeals to niche markets and commands premium pricing. Bioengineered purple tomatoes achieve high anthocyanin levels through the introduction of snapdragon transcription factors, while classically bred 'Indigo Rose' purple tomatoes are developed via classical breeding methods, providing an alternative for consumers who prefer traditionally bred products. Specifically, the purple tomato holds …

African Sleeping Sickness: From Basic Biology To Future Directions, Riddhi R. Patel

All Theses

African Sleeping Sickness is a Neglected Tropical Disease (NTD) which poses a significant health risk to impoverished populations in 36 Sub-Saharan African countries. It is a devastating disease caused by the protozoan parasite Trypanosoma brucei, which is transmitted to mammals via the bite of infected tsetse flies. The disease manifests in two stages: the hemolymphatic stage and the meningoencephalitic stage. In the latter stage, it invades the Central Nervous System (CNS) and can be fatal if left untreated. It is caused by morphologically indistinguishable species of Trypanosoma brucei in both humans and animals, where in humans it is known as …

A Stakeholder-Informed Conceptual Framework For Evaluating Genomics In Precision Oncology, Julie A. Wiedower

All Dissertations

This dissertation explores the value of genomic testing in precision oncology with an emphasis on how US payers conceptualize and prioritize elements of value. This research aims to address gaps in understanding payer perspectives and proposes a stakeholder-informed framework for evaluating genomic testing in oncology. To achieve this aim, the presented research investigates payer perspectives, value-based cancer care priorities, and the conceptual understanding of the value of a genetic diagnosis to establish a framework for value with the payer audience in mind. Chapter 1 outlines relevant background information relating to the genomic revolution and challenges in translating genomic testing technologies …

The Genomic Landscape And Prognostic Impact Of Kras, Stk11, And Smarca4 Mutations And Co-Mutations On Survival Outcomes In Non-Small Cell Lung Cancer, Peter Manolakos

All Dissertations

Non-small lung cancer (NSCLC) accounts for 85% of lung cancer cases, and Kirsten rat sarcoma viral oncogene homolog (KRAS), Serine/Threonine Kinase 11 (STK11), and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutations and co-mutations have been increasingly recognized for their potential prognostic significance. However, clear knowledge gaps remain regarding which treatments should be selected for patients who present clinically with KRAS/STK11 or KRAS/SMARCA4 co-mutations, as outlined in Chapter 1. Despite significant clinical development advancements in immunotherapy and targeted therapy, a deeper understanding of the influence of these genomic …

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 …

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 …

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 …

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 …

Characterization Of Ato Family Transporters In The Fungal Pathogen Cryptococcus Neoformans, Will Betsill

All Theses

Fungal pathogens are a significant threat to public health as they are becoming increasingly common and more resistant to treatment. Cryptococcus neoformans contributes greatly to this threat annually by causing an estimated 278,000 cases of cryptococcal meningitis resulting in approximately 181,000 deaths globally according to the CDC. C. neoformans is ubiquitous across most of the globe and can be found in such places as in trees or soil. Exposure to this fungus is especially dangerous to individuals who are immunocompromised or immunosuppressed. In these cases, inhalation of spores can lead to infection in the lungs. Once in the lungs, C. …

Identification And Characterization Of Geotrichum Candidum Isolates From Peach With Reduced Sensitivity To Propiconazole, Sara Price

All Theses

Geotrichum candidum Link (1809) is a yeast-like fungus that causes sour rot of stone fruits, including peach (Prunus persica). The disease caused damage between 2021 and 2023 to the peach crop kept in cold storage at a commercial farm in South Carolina despite preharvest and postharvest applications of fungicides. Isolates from 41 symptomatic fruit, from a South Carolina (SC) commercial packing house, as well as other isolates obtained from South Carolina were identified to be G. candidum based on species-specific PCR amplifications of the β tubulin gene. Commonly used postharvest fungicide fludioxonil had no effect on G. candidum mycelial growth …

Elucidating Mechanisms Of Rad51 Regulation During The Replication Stress Response, Alexandra Hawks

All Dissertations

The genome must be accurately and efficiently replicated each cell cycle to ensure there is not accumulation of mutations or structural rearrangements. When an active replication fork stalls, there are multiple DNA damage tolerance (DTT) pathways that can act to both protect integrity of DNA at the fork and restart replication. RAD51, a vital recombinase, works with HLTF, ZRANB3, and SMARCAL1 or FBH1 to regress stalled replication forks. RAD51 is loaded and stabilized onto the replication fork to protect the newly synthesized DNA from degradation. RAD51 is also active during the template switching DDT pathway. This pathway can be utilized …

Methyltransferase, Glucose Adaptation, And Import Complex In Trypanosoma Brucei, Emily Knight

All Dissertations

Trypanosoma brucei is a kinetoplastid parasite responsible for human African trypanosomiasis (HAT) and nagana, a livestock wasting disease, which both endemic to sub-Saharan Africa. Unique to kinetoplastids are the specialized peroxisomes, named glycosomes, which compartmentalize the first several steps of glycolysis and gluconeogenesis, nucleotide sugar biosynthesis, and many other metabolic processes. Kinetoplastids are unique in that they have a single mitochondrion. In this work, I present the first study into SET domain proteins in any kinetoplastid parasites. We have characterized a predicted SET domain protein, TbSETD3, that localizes to the mitochondrion and a depletion of the protein results in growth …

Diagnosis Of Urinary Tract Infections And Rapid Molecular Characterization Of Antibiotic Resistance, Mohammed Harris

All Dissertations

Urinary tract infections (UTIs) are one of the most common infectious clinical entities in both community and hospital settings. They have a broad range of clinical severity yet inflict large epidemiological burden of morbidity and mortality on patients and the healthcare system with billions of dollars in cost of treatment. Understanding what methods are optimal for diagnosing UTIs are critical to mitigate the marked impact and cost of these infections.

Chapter 1 and 2 in this work surveys the broad array of diagnostic modalities for UTIs and highlights their advantages and limitations in the context of the current standard of …

A Multi-Pronged Investigation To Identify Genes Affecting The Autoregulation Of Nodulation: Lasercapture Microdissection And The Barely Any Meristem Gene Family In Medicago Truncatula, Jacklyn Thomas

All Dissertations

The unique evolutionary adaptation of legumes for nitrogen-fixing symbiosis leading to nodulation is tightly regulated by the host plant. One pathway negatively regulates the number of nodules formed in response to the metabolic status of the shoot (carbon) and root (nitrogen); this long-distance systemic regulation is the autoregulation of nodulation (AON) pathway. AON is a root to shoot pathway that allows the plant to limit the number of nodules formed on roots. Central to the receptor complex in the shoots is a leucine-rich-repeat receptor-like kinase (LRR-RLK) called MtSUNN mutation of which results in plants with too many nodules. SUNN …

Investigating The Biochemical Properties Of A Novel Mutation, A194v, In Human Rad51, Briana Vollbeer

All Theses

DNA double-strand breaks (DSB) are one of the most serious DNA lesions because improper repair of a DSB can lead to loss of heterozygosity, aneuploidy, and cancer. One of the primary pathways to repair DSBs is homologous recombination (HR). HR resects the DNA around the DSB and then uses homologous DNA as a template to restore the broken sequence. RAD51 has a vital function in this pathway by forming a nucleoprotein filament on a resected end of the DSB. The nucleoprotein filament searches for homology within the homologous DNA. Once homology is located, strand invasion followed by strand exchange occurs. …