Life Sciences Commons^™

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Circadian Rhythmicity And Melatonin Sensitivity In The Human Gut Commensal Bacterium Klebsiella Aerogenes, Kinga Graniczkowska

Theses and Dissertations--Biology

While the expression of circadian rhythms is nearly universal among multicellular eukaryotic organisms, demonstration of this phenomenon in prokaryotes has been largely restricted to photosynthetic cyanobacteria until very recently. Further, growing interest in gastrointestinal microbiomes has revealed a complex temporal relationship between the gastrointestinal clock and the bacterial microbiome within. At least one member of the gut microbiome, Klebsiella (née Enterobacter) aerogenes, responds to the indoleamine hormone melatonin, secreted by the gastrointestinal system itself. Further research revealed that K. aerogenes also expresses a circadian rhythm in motility and gene expression that is temperature compensated. Although rhythmicity is unaltered …

Mechanisms Of Cadmium-Induced And Epidermal Growth Factor Receptor Mutation-Driven Lung Tumorigenesis, Hsuan-Pei Lin

Theses and Dissertations--Toxicology and Cancer Biology

Cadmium (Cd) is a ubiquitous pollutant in the environment and a known carcinogen for lung cancer. Cd has been shown to act as a weak mutagen, which suggests that it may exert tumorigenic effect through non-genotoxic ways, such as epigenetic mechanisms. The goal of this project is to investigate the mechanisms of Cd carcinogenesis focusing on the role of lncRNA dysregulations. The Cd-exposed cells formed significantly more colonies in soft agar, displayed cancer stem cell (CSC)-like property and formed tumors in nude mice. Mechanistically, the lncRNA microarray analysis revealed that chronic Cd exposure dysregulates lncRNA expressions. Q-PCR analysis confirmed the …

Genetic Mouse Models Of Liver Disease: Potential Roles Of Zhx2 (Afr1) And Afr2 In Damage And Regeneration, Courtney P. Turpin

Theses and Dissertations--Pharmacology and Nutritional Sciences

The liver is the largest internal organ in mammals and responsible for carrying out various processes, including lipid and carbohydrate metabolism, detoxification of chemicals, and production of serum proteins. Liver damage, which can be caused by a variety of agents including viral infection, environmental toxins, alcohol and excessive dietary fats, can cause dysregulation of these critical functions, leading to worsening liver pathophysiology and impacting health. However, the liver has the remarkable ability to regenerate when damaged. Hepatocytes, which comprise a majority of liver cells, are relatively quiescent under healthy conditions. Upon injury, remaining hepatocytes can proliferate to recover from liver …

Distribution And Diversity Of Heliothine And Other Lepidopteran Nudiviruses, Emrah Ozel

Theses and Dissertations--Entomology

Helicoverpa zea nudivirus 2 (HzNV-2) is the only known sterilizing and sexually-transmitted insect virus and causes pathological symptoms in H. zea reproductive tissues. HzNV-2 has features that make it a candidate as a H. zea (corn earworm) control agent, such as the ability to cause asymptomatic (latent) and symptomatic (lytic) infections and the ability to influence mating behavior of its host to favor virus spread. HzNV pathology has been studied and its genome sequenced, however, its prevalence in natural populations is largely unknown. In this study, we developed and used a low-cost PCR-based molecular survey to investigate HzNV-2 prevalence and …

Novel Computational Methods For Cancer Genomics Data Analysis, Jinpeng Liu

Theses and Dissertations--Computer Science

Cancer is a genetic disease responsible for one in eight deaths worldwide. The advancement of next-generation sequencing (NGS) technology has revolutionized the cancer research, allowing comprehensively profiling the cancer genome at great resolution. Large-scale cancer genomics research has sparked the needs for efficient and accurate Bioinformatics methods to analyze the data. The research presented in this dissertation focuses on three areas in cancer genomics: cancer somatic mutation detection; cancer driver genes identification and transcriptome profiling on single-cell level.

NGS data analysis involves a series of complicated data transformation that convert raw sequencing data to the information that is interpretable by …

Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development, Megan Weaver

Theses and Dissertations--Biology

Vertebrate retinal development requires timely and precise fusion of the optic fissure. Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed optic fissure fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a^-/- embryos fail to accumulate F-actin in the optic fissure prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a^-/- embryos. When examining the connection …

Periocular Mesenchyme Heterogeneity During Morphogenesis Of The Vertebrate Ocular Anterior Segment, Kristyn L. Van Der Meulen

Theses and Dissertations--Biology

The vertebrate eye is a complex organ, responsible for the primary sense with which we interact with our environment: vision. Development of the eye is a tightly regulated process, controlled by a vast network of genes. This process begins with eye morphogenesis, when the eye structure is formed through a series of morphogenetic movements and culminates in the creation of the optic cup, lens, and presumptive optic stalk. Next, retinal differentiation creates the critical cell layers of the retina needed to process light waves that enter the eye, including rod and cone photoreceptors, interneurons, and support cells. Failure in either …

Southern Pine Beetle-Specific Rna Interference Demonstrates No Effects On Nontarget Insects, Hannah Marie Hollowell

Theses and Dissertations--Entomology

The endemic southern pine beetle (SPB), Dendroctonus frontalis Zimmermann, is a highly destructive bark beetle that has devastated coniferous forests of the southern United States for decades. Traditional management strategies have been unable to respond effectively to largescale SPB outbreaks, prompting exploration of novel techniques including RNA interference (RNAi). Double-stranded RNAs (dsRNAs) are effective at triggering gene silencing and inducing mortality in SPB, but determining delivery methods and demonstrating specificity of the treatments is necessary before this technology may progress to deployment.

I evaluated three SPB-specific dsRNAs on model nontarget insects to assess potential lethal effects, sublethal effects such as …

Leveraging Transcriptomic Approaches To Identify Differences In Genetic Programming Driving Two Distinct Wound Healing Mechanisms, Regeneration And Fibrosis, In Acomys And Mus, Shishir K. Biswas

Theses and Dissertations--Biology

Why can some animals and others cannot? This fundamental question has fueled scientists studying regeneration for hundreds of years since early observations in crayfish, salamanders and many other organisms. While most contemporary work in regeneration is done in a handful of species including salamanders, zebrafish and flatforms, these organisms lack a closely-related, non-regenerating sister species from which unique genetic differences can be identified. Additionally, while much has been learned from these organisms, they do not share fundamental biological traits with mammals (endothermy, metabolism and immune system) which limits the ability to translate this research for clinical medicine. To this end, …

Leveraging Chemical And Computational Biology To Probe The Cellulose Synthase Complex, B. Kirtley Amos

Theses and Dissertations--Plant and Soil Sciences

Cellular expansion in plants is a complex process driven by the constraint of internal cellular turgor pressure by an expansible cell wall. The main structural element of the cell wall is cellulose. Cellulose is vital to plant fitness and the protein complex that creates it is an excellent target for small molecule inhibition to create herbicides. In the following thesis many small molecules (SMs) from a diverse library were screened in search of new cellulose biosynthesis inhibitors (CBI). Loss of cellular expansion was the primary phenotype used to search for putative CBIs. As such, this was approached in a forward …