Life Sciences Commons^™

Phenotypic And Transcriptomic Characterization Of Colonial Phase Variation In The Cholera Pathogen Reveals A Novel Smooth Biofilm-Defective Form, Bliss Nicole Lambert

LSU Doctoral Dissertations

Biofilm formation, through the production of Vibrio polysaccharide (VPS), greatly enhances the environmental fitness and pathogenic success of Vibrio cholerae. As a result of phase variation, V. cholerae can switch from a smooth form to rugose, whose cells produce excess VPS, resulting in highly structured biofilms and greater resistance to stress. To further characterize the reversible process of phase variation, we isolated three colonial lineages. Each lineage began with a smooth parent, N16961, and contained a rugose variant derived from the parent, N16961R, as well as a smooth revertant of the rugose, N16961SD. We found clear phenotypic and transcriptomic …

Harnessing The Anopheles Microbiome To Conditionally Express Anti-Plasmodial Effectors During The Blood Meal, Jackie Shane

Electronic Theses and Dissertations

The control of vector-borne diseases such as malaria has been an extremely important research subject for hundreds of years. Because of the complex lifecycles of the pathogens that cause these diseases, finding a comprehensive treatment or preventative strategy has proven extremely difficult. Malaria alone is responsible for almost half a million deaths annually, most of them children under 5 years old. This disease is caused by parasitic protists in the genus Plasmodium that are transmitted to humans from Anopheles sp. mosquitoes. Most preventative strategies that are in use today revolve around controlling the vectors, including bed nets, insecticides, and larval …

Understanding The Impacts Of Current And Future Environmental Variation On Central African Amphibian Biodiversity, Courtney A. Miller

University of New Orleans Theses and Dissertations

Global climate change is projected to impact multiple levels of biodiversity by imposing strong selection pressures on existing populations, triggering shifts in species distributions, and reorganizing entire communities. The Lower Guineo-Congolian region in central Africa, a reservoir for amphibian diversity, is predicted to be severely affected by future climate change through rising temperatures and greater variability in rainfall. Geospatial modelling can be used to assess how environmental variation shapes patterns of biological variation – from the genomic to the community level – and use these associations to predict patterns of biological change across space and time. The overall goal of …

Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li

Arts & Sciences Electronic Theses and Dissertations

The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is …

Mechanistic Characterization Of Resistome And Microbiome Dynamics Across Diverse Microbial Habitats, Andrew John Gasparrini

Arts & Sciences Electronic Theses and Dissertations

Increasing antibiotic resistance in pathogens is a serious public health challenge, with over two million antibiotic resistant infections in the United States leading to at least 23,000 deaths and an estimated $55 billion in excess healthcare and societal costs. Antibiotic resistance has risen steadily in both pathogenic and benign bacteria since antibiotics’ introduction to agriculture and medicine 70 years ago. A dramatic reduction in the number of antibiotics approved for human use has accompanied this rise in antibiotic resistance, leading to the alarming prospect of a post-antibiotic era. Understanding the evolutionary origins, genetic contexts, and molecular mechanisms of antibiotic resistance …

Grammar And Variation: Understanding How Cis-Regulatory Information Is Encoded In Mammalian Genomes, Dana Michele King

Arts & Sciences Electronic Theses and Dissertations

Understanding how genotype leads to phenotype is key to understand both the development and dysfunction of complex organisms. In the context of regulating the gene expression patterns that contribute to cell identity and function, the goal of my thesis research is to how changes in genome sequence may impact impact gene expression by determining how sequence features contribute to regulatory potential. To accomplish this goal, I first leveraged the key regulatory role of pluripotency transcription factors (TFs) in mouse embryonic stem cells (mESCs) and tested synthetically generated and genomic identified combinations of binding site for four TFs, OCT4, SOX2, KLF4, …

A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey

Arts & Sciences Electronic Theses and Dissertations

The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …

Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal

Arts & Sciences Electronic Theses and Dissertations

The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific …

The Role Of Fibrillin-1 In Eye Development And Disease, Wendell Brooks Jones

Arts & Sciences Electronic Theses and Dissertations

The ciliary zonule of the human eye consists of a circumferential array of fibers that connect the ocular lens to the nonpigmented ciliary epithelium (NPCE) located at the inner wall of the eye. Zonular fibers consist of bundles of beaded filaments called microfibrils. Microfibrils are major structural elements of the extracellular matrix and are present in pure form in the ciliary zonule. Microfibrils are composed principally of fibrillin-1 (FBN-1); a large extracellular matrix glycoprotein. In humans, mutations in FBN1 underlie Marfan syndrome; a pleiotropic connective tissue disorder that profoundly affects the eye. Ocular manifestations include ectopia lentis (dislocated lenses), cataracts, …

Red Panda: A Novel Method For Detecting Variation In Single-Cell Rna Sequencing, Adam Cornish

Theses & Dissertations

Single-cell sequencing enables the rapid acquisition of genomic and transcriptomic data from individual cells to better understand genetic diseases, such as cancer or autoimmune disorders, which are often affected by changes in rare cells. Currently, no existing software is aimed at identifying single nucleotide variations or micro (1-50bp) insertions and deletions in single-cell RNA sequencing (scRNA-seq) data. However, generating high quality data is vital to the study of the aforementioned diseases, among others. Our goal is to create such a tool and use in-house sequencing to validate its effectiveness. Our software employs the unique information found in scRNA-seq data to …

Physella Acuta, Comparative Immunology And Evolutionary Aspects Of Gastropod Immune Function, Jonathan H. Schultz

Biology ETDs

Gastropod immunobiology has benefitted from investigations focused on the planorbid snail Biomphalaria glabrata, intermediate host for the human parasite Schistosoma mansoni. Though such concentrated efforts have elucidated fascinating aspects of invertebrate immunity, they have not provided full knowledge regarding the evolution of immune function among other gastropod species. This dissertation presents the importance of making strategic choices regarding which organisms to select for comparative immunology. Herein, the choice was made to investigate the immunobiology of Physella acuta, a freshwater snail species of the Physidae, a sister family to Planorbidae to which B. glabrata belongs. Benefiting greatly from …

Accumulation And Transmission Dynamics Of A Naturally-Occurring Mtdna Deletion In Caenorhabditis Briggsae, Jennifer Anne Sullins

Dissertations and Theses

Maintaining mitochondrial genome sequence integrity is essential for preserving normal mitochondrial function. Several human diseases have been associated with heteroplasmic mitochondrial genome mutations, but few genetic systems can simultaneously represent pathogenic mitochondrial genome evolution and inheritance. The nematode Caenorhabditis briggsae is one such model. Natural C. briggsae isolates are globally-distributed and phylogenetically grouped into three distinct clades, with isolates exhibiting varying levels of a large-scale mtDNA deletion, nad5∆. Furthermore, a small subset of clade II isolates exhibits putative compensatory mutations that may reduce the risk of deletion formation and accumulation in those populations. In this thesis, the author characterizes the …

Investigating The Role Of Brachypodium Distachyon Cellulose Synthase 8 In Gluconacetobacter Diazotrophicus Colonization, Xuan Yang

Electronic Thesis and Dissertation Repository

Nitrogen is an essential nutrient for plant growth. Significant amount of nitrogen fertilizer is applied to crop field to maintain high yield. Alternatives to chemical nitrogen fertilizer are needed to reduce the costs of crop production and offset environmental damage. Gluconacetobacter diazotrophicus is a nitrogen fixing bacterium that was originally isolated from sugarcane and has been proposed as a possible biofertilizer for monocot crop production. However, the colonization of G. diazotrophicus in most monocot crops is limited and deep understanding of the response of the host plants to G. diazotrophicus colonization is still lacking. In this study, research was conducted …

Sip-428, A Sir2 Deacetylase Enzyme And Its Role In Biotic Stress Signaling Pathway, Bal Krishna Chand Thakuri

Electronic Theses and Dissertations

SABP2 (Salicylic Acid Binding Protein 2) plays a vital role in the salicylic acid signaling pathway of plants both regarding basal resistance and systemic acquired resistance against pathogen infection. SIP-428 (SABP2 Interacting Protein-428) is a Silent information regulator 2 (SIR2) like deacetylase enzyme that physically interacts with SABP2 in a yeast two-hybrid interaction and confirmed independently by a GST pull-down assay. We demonstrated that SIP- 428 is an NAD+ dependent SIR2 deacetylase enzyme. Transgenic tobacco plants silenced in SIP- 428 expression via RNAi showed enhanced basal resistance to microbial pathogens. Moreover, these SIP-428-silenced lines also exhibited a robust induction of …

Genetic Evolution And Prognostic Determinants Of Pancreatic Cancer On Longitudinal Liquid Biopsies, Vincent Bernard

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates amongst solid tumors. As early detection of PDAC is unusual and typically incidental, most patients present with locally advanced and metastatic disease where effective therapeutic strategies remain a significant unmet need. Specifically, surrogate biomarkers for tumor monitoring of PDAC may lead to improved elucidation of clinical actionability and prognostic potential. On the other hand, tumor tissue is rarely sampled in patients presenting with de novo or recurrent metastatic PDAC, apart from a fine needle aspiration or a core needle biopsy performed for diagnosis. This precludes the opportunity for …

Investigating Autophagy Dysfunction Induced By A Parkinson's Disease-Causing Mutation In Vps35, Abir Ashfakur Rahman

Boise State University Theses and Dissertations

Parkinson’s Disease (PD) is an idiopathic disorder with no known cure. With number of cases steadily rising around the world, it is imperative to turn to the underlying cellular and molecular mechanisms of the disease manifestation and neurodegeneration to craft novel modes of therapy. VPS35 is one of the few genes that have identified and definitively linked to familial PD. The particular mutation that has been associated is known to cause dysfunction of a key cellular process known as autophagy. This process is primarily responsible for clearance of unwanted, damaged or misfolded proteins, among other things. Our study reveals an …

The Evaluation Of Genetic And Phenotypic Differences Associated With Short Term Selection Of Four Different Feed Efficiency Strategies In Japanese Quail, Alex David Gilley

Graduate Theses and Dissertations

The concept of feed efficiency (FE), one unit of feed required to improve one unit of desired output, is relatively simple. However multiple outputs are desired in a commercial poultry breeding program, resulting in the need for nutrients to be partitioned in a particular manner. At the broadest level, nutrients are partitioned between production and maintenance requirements. The requirements for production and maintenance varies between birds. It is the poultry breeder’s responsibility to select individuals most aligned with the breeding objective. Irrespective of the breeding objective, various related and non-related traits influence a bird’s FE. To effectively improve FE, the …

Improving Dbnsfp, Mingyao Lu

Dissertations & Theses (Open Access)

IMPROVING dbNSFP

Mingyao Lu, B.S.

Advisory Professor: Xiaoming Liu, Ph.D.

The analysis and interpretation of DNA variation are very important for the Whole Exome studies (WES). Genome research has focused on single nucleotide variants (SNVs). Since indels are as important as SNVs, especially indels in coding regions are often candidates of disease-causing variants, thus, it is necessary to expand the focus to include indel mutations.

The goal of my project is to provide an automatic annotation pipeline to the WES based disease studies project by extending the dbNSFP with a tool for automated indel annotation and deleteriousness prediction. The current …

Genetic And Epigenetic Investigations On Pulmonary Hypertension Syndrome In Meat Type- Chickens, Khaloud Alzahrani

Graduate Theses and Dissertations

This dissertation presents a collection of studies that investigate the genetic and epigenetic associations to ascites phenotype in broiler chickens. Ascites is a significant metabolic disease associated with fast-growing meat-type chickens (broilers) and is a terminal result of pulmonary hypertension syndrome PHS. It is a multi-factorial syndrome caused by interactions between genetic, physiological, environmental, and managemental factors. It was estimated that ascites accounts for losses of about US$1 billion annually worldwide and for over 25% of broilers mortality. Although traditional and molecular genetic methods in the selection and in performance improvements, has greatly reduced ascites frequency, yet it has not …

Evaluation Of Genetic And Environmental Influences On Broiler Meat Quality, Sara Katherine Orlowski

Graduate Theses and Dissertations

The effect of both genetic and environmental influences on broiler meat quality were evaluated over three experiments. Selection response was assessed for broiler lines selected for high (HBY4) and low (LBY4) four day percentage breast yield which were formed from a random bred control (RAN). A modern random bred population (MRB) created in 2015 was evaluated for differences in 4 day percentage breast yield and the resulting differences in the incidence and severity of the woody breast and white striping myopathies. Additionally, the use of embryonic thermal manipulation to impact cell division and early caloric feed restriction to slow growth …

Temperature And Polyunsaturated Fatty Acid’S Effect On Daphnia Magna Reproduction, Mark Albright

Electronic Theses and Dissertations

Organisms adapt to their environments by adjusting their biochemistry and physiology; such adaptation is limited by resource availability and physiological constraints. The freshwater crustacean Daphnia magna inhabits a wide range of environments and must survive and reproduce within a range of temperatures. One limit to low-temperature adaptation is thought to be the availability of unsaturated fatty acids necessary to maintain proper fluidity of cellular membranes. D. magna maintained at 10 ºC on a diet poor in unsaturated fatty acids have been observed to produce clutches that fail to develop. However, this has not been observed on a diet rich in …

Identification And Functional Characterization Of Effectors From An Anther Smut Fungus, Microbotryum Lychnidis-Dioicae., Venkata Swathi Kuppireddy

Electronic Theses and Dissertations

Microbotryum lychnidis-dioicae causes anther smut fungus in its host plant, Silene latifolia. The goal of this work is to identify and characterize the virulence determinants of this pathogen to better understand the molecular basis behind this host-pathogen interaction. This work studied for the first time the key effectors in the mechanism of infection by this fungal species. Using, yeast two-hybrid screens, I have identified the host plant interaction partners for the effector, MVLG_01732. A second effector MVLG_05720, interacts with other fungal proteins that appear to facilitate the fungal establishment and colonization during the infection. Our findings indicate that a …

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations & Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Acetylation Profiles Of Histone And Non-Histone Proteins In Breast Cancer, Alla Karpova

McKelvey School of Engineering Theses & Dissertations

This study evaluates the impact of protein acetylation on breast cancer gene expression and the regulation of metabolism. Acetylation is the second abundant post-translational modification after phosphorylation, regulating protein activity and function. The alterations in acetylation of both histone and non-histone proteins is known to be related to many human diseases, including cancer. Acetylation and deacetylation of histones is closely associated with the regulation of gene expression, while acetylation of non-histone proteins may have a broad effect on major cellular processes, such as proliferation, metabolism, cell cycle and apoptosis, imbalanced regulation of which is essential for cancer development. Therefore, it’s …

Thermal And Microbial Effects On Brown Macroalgae: Heat Acclimation And The Biodiversity Of The Microbiome, Charlotte Tc Quigley

Electronic Theses and Dissertations

This dissertation examines effects of stress on brown algal biology from a macroscopic scale by examining the whole aquaculture crops, and at a microscopic level by examining the macroalgal microbiome, across the vertical stress gradient of the intertidal zone and across the latitudes of their biogeographic ranges. Thermal stress negatively affected seedstock gametophytes of the kelp Alaria esculenta isolated from northern and southern locations in Maine. However, previous thermal stress had a positive effect on growth of the next-generation sporophytes. Alaria esculenta has potential as a kelp crop in Maine’s sea vegetable aquaculture sector and implementing this protocol may allow …

Speciation And Hybridization In Jamaican-Endemic Streamertail Hummingbirds (Trochilus Polytmus And T. Scitulus), Caroline D. Judy

LSU Doctoral Dissertations

Streamertails hummingbirds (Trochilus polytmus and T. scitulus) are recently diverged sister taxa that appear to have speciated in situ on the island of Jamaica. They are distinguished by male bill color, a secondary sexual trait that is coral red in T. polytmus and jet black in T. scitulus. They hybridize in a narrow zone where their ranges meet in eastern Jamaica. In Chapter 2, I performed a formal population survey of T. scitulus to determine the size of the population, which was unknown. I determined that the total population contains well over 100,000 individuals despite its limited …

Spatial And Temporal Patterns Of Neutral And Adaptive Genetic Variation In The Alpine Butterfly, Parnassius Smintheus, Maryam Jangjoo

Electronic Thesis and Dissertation Repository

Understanding how much genetic diversity exists in populations, and the processes that maintain that diversity, has been a central focus of population genetics. The evolutionary processes that determine patterns of genetic diversity depend on underlying ecological processes such as dispersal and changes in population size. In this thesis, I examine the influence of dispersal and population dynamics on neutral and adaptive genetic variation in a naturally occurring network of populations of the alpine butterfly, Parnassius smintheus.

My first objective was to determine the combined consequences of demographic bottlenecks and dispersal on neutral genetic variation within and among populations. Using …

An Integrative Approach To Understanding Morphological Novelties: Anatomy, Development, Genetics, And Evolution Of An Extreme Craniofacial Trait In East African Cichlids, Moira R. Conith

Doctoral Dissertations

Phenotypic novelties are an important but poorly understood category of morphological diversity that are often associated with elevated rates of diversification and/or ecological success. The aim of this dissertation is to explore a phenotypic novelty at many levels to contribute to our understanding of how these unique traits can arise (e.g., genetically, developmentally, and evolutionarily) as well as their ecological consequences (e.g., trait function). The extreme snout of the Lake Malawi cichlid fish Labeotropheus is used as a case study. The first chapter establishes the Labeotropheus snout as a model of phenotypic novelty by characterizing the gross morphology, genetic architecture, …

A Plant Pathology View Of Signaling: A Computational Study Of Fusarium Oxysporum Kinomes And Downy Mildew Resistance In Sweet Basil, Gregory Deiulio

Doctoral Dissertations

This dissertation is composed of two projects that focus on pathogen and plant signaling within the framework of plant pathology. The first project targets protein kinases within the species complex Fusarium oxysporum based on genomic information and tracks their presence/absence and copy number variation across evolutionary time. We have predicted the kinomes of 19 Ascomycete fungi using the kinase annotating software Kinannote. Among Fusaria, kinases related to the perception of the environment, such as Histidine kinases, are proliferated. Similarly, I observed the expansion of Target of Rapamycin (TOR) kinase that regulates cell growth and development in responding to environmental cues. …

Population Genetics Of The Eastern Subterranean Termite, Reticulitermes Flavipes, In The Southern Appalachian Mountains, Lee Ann Passarella

Honors Theses

As an area rich in biodiversity, the Appalachian Mountains are an ideal place for biological research. The pronounced impacts of Pleistocene climatic cycles on forest distributions over time have shaped the evolutionary history of animals that depend on these habitats, underpinning the research that is presented here. The present study on the eastern subterranean termite, Reticulitermes flavipes, was conducted to better understand the spatial distribution of genetic diversity within and among populations of this species in the context of the aforementioned historical climatic changes in the southern Appalachian Mountain region. I hypothesized that there would be geographically localized, distinct genetic …