Genomics Commons^™

Development Of An In Vitro Model Of Mitochondrial Dna Copy Number Depletion Via Stable Inducible Expression Of D1135a Mutant Dna Polymerase Gamma, Amanda L. Morin

Electronic Thesis and Dissertation Repository

Mitochondria are responsible for several crucial cellular processes and contain their own DNA (mtDNA) that exists in several copies. Variation of mtDNA copy number (mtDNA-CN) alters energy metabolism and can modify the epigenome and transcriptome. We hypothesized that inducible expression of polymerase-deficient D1135A dominant-negative DNA polymerase gamma (DN-POLG) would result in mtDNA-CN depletion. Here, an in vitro model expressing D1135A POLG was created using the Flp-InTM T-RExTM-293 stable inducible expression system. Stable integration was confirmed with PCR amplification and Sanger sequencing of post-integration genomic sequences. D1135A POLG expression was confirmed with Western blot of the FLAG-tag antibody. Induction of D1135A …

Illuminating The Drivers Of Genomic Diversification In Lamprologine Cichlids Of The Lower Congo River, Naoko P. Kurata

Dissertations, Theses, and Capstone Projects

Freshwater fishes are extraordinarily diverse, considering their available habitats represent a tiny proportion of the earth’s surface. Rivers connect heterogeneous habitats in a linear form and provide excellent simplified models to understand how aquatic biodiversity evolves. In particular, the lower Congo River (LCR) in west Central Africa consists of a dynamic hydroscape exhibiting extraordinary aquatic biodiversity, endemicity, and morphological and ecological specialization. This system is thus an excellent natural laboratory for understanding complex speciation and population diversification processes. In my research, I explore various drivers of diversification, and adaptive evolution in rheophilic lamprologine cichlids endemic to the LCR, including Lamprologus …

The Genomic Dynamics Of Fermented Food Microbes, Katherine Chacón-Vargas

Doctoral Dissertations

Along with the agriculture and domestication revolution, humans have utilized bacteria, yeasts, and molds for millennia in the production of traditionally fermented foods and beverages. Fermentation is a very ancient practice of high relevance nowadays since it contributes with a great variety of foods worldwide. Microbial fermentation allows metabolic transformation of the raw food materials leading to biochemical changes that played a key role in food preservation, health benefits, nutrition, flavors, and texture, among others. Food fermentation practices could diverge from traditional artisanal spontaneous fermentation to industrialize methods with specialized microbial starters and although fermented environments tend to be very …

Spatiotemporal Transcriptome Diversity And Responses To Salinity Tolerance In The Extremophyte Schrenkiella Parvula, Chathura Wijesinghege

LSU Doctoral Dissertations

Schrenkiella parvula is an extremophyte model related to the most widely studied plant model, Arabidopsis thaliana and Brassica crops in the mustard family (Brassicaceae). It can thrive in highly saline environments where the soil is enriched in Na⁺, K⁺, Li⁺, borates, and chlorides. Understanding how this extremophyte can survive high salinity with genomic adaptations can provide insight into developing stress resilient crops in the future. Gene expression of S. parvula in response to salt has been investigated using shoot and root tissue from mature vegetative-phase plants. However, prior studies have not examined the transcript …

Changes In Gene Expression From Long-Term Warming Revealed Using Metatranscriptome Mapping To Fac-Sorted Bacteria, Christopher A. Colvin

Masters Theses

Soil microbiomes play pivotal roles to the health of the environment by maintaining metabolic cycles. One question is how will climate change affect soil bacteria over time and what could the repercussions be. To answer these questions, the Harvard Forest Long-Term Warming Experiment was established to mimic predicted climate change by warming plots of land 5℃ above ambient conditions. In 2017, 14 soil core samples were collected from Barre Woods warming experiment to mark 15 years since the establishment of the soil warming in that location. These samples underwent traditional metatranscriptomics to generate an mRNA library as well as a …

Chemosensory Receptors In Berghia Stephanieae: Bioinformatics And Localization, Kelsi L. Watkins

Masters Theses

Chemosensation is achieved through the binding of chemical signals to chemoreceptor proteins embedded in the membranes of sensory neurons. The molecular identity of these receptors, as well as the downstream processing of chemosensory signals, has been well studied in arthropods and vertebrates. However, very little is known about molluscan chemosensation. The identity of chemoreceptor proteins in the nudibranch mollusc Berghia stephanieae are unknown. Data from other protostome and molluscan studies suggest Berghia may use ionotropic receptors for some forms of chemoreception. This study used a bioinformatics approach to identify potential chemosensory ionotropic receptors in the transcriptome of Berghia. A …

What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu

Doctoral Dissertations

Over the past decade, single-cell technologies evolved from profiling hundreds of cells to millions of cells, and emerged from a single modality of data to cover multiple views at single-cell resolution, including genome, epigenome, transcriptome, and so on. With advance of these single-cell technologies, the booming of multimodal single-cell data creates a valuable resource for us to understand cellular heterogeneity and molecular mechanism at a comprehensive level. However, the large-scale multimodal single-cell data also presents a huge computational challenge for insightful integrative analysis. Here, I will lay out problems in data integration that single-cell research community is interested in and …

Haplotype-Informed Allelic Imbalance Detection From Rna In Cancer, Zuhal Ozcan

Dissertations & Theses (Open Access)

Comprehensive genomic and transcriptomic characterization of tumors has uncovered enrichment for distinct aneuploidy and expression patterns, demonstrating the utility of molecular based classification of cancers and their subtypes. Existing cohorts with transcriptomic profiling from next-generation sequencing contain an untapped potential to also relate genomics with rich clinical phenotypes. Yet, derivation of somatic copy number and expression profiles from analyses of RNA has remained elusive. Further, DNA analysis in these cohorts is not always feasible due to limited tissue availability or financial constraints. Here, we present a statistical approach that overcomes these challenges using haplotype information to aid detection of somatic …

Neonatal Islet-1+ Cardiovascular Progenitor Cell-Derived Exosomes And Their Functional Ability To Regulate Proliferation, Lourdes Ceja

Electronic Theses, Projects, and Dissertations

Heart failure affects many people around the world and can lead to disease progression and death. Consequently, new stem and exosome-based therapies are needed to address this major health issue and to provide therapeutic options that will improve outcomes for the increasing number of patients with heart disease. Stem cell-derived exosomes have captivated researchers’ attention over the past couple of years based on their functional role in cellular signaling which highlights the vital component of the secretome of stem and progenitor cells. Since neonates have significantly enhanced regenerative ability, we hypothesized that exosomes isolated from Islet-1+ expressing neonatal human cardiovascular …

Functional Role Of Ppal And Potential For Moss In Industrial Applications., Susana Perez Martinez

Electronic Theses and Dissertations

This dissertation is an examination and characterization of the functional roles of PPAL. PROTEIN PRENYLTRANSFERASE ALPHA SUBUNIT-LIKE (PPAL) is a recently discovered gene. PPAL homologs are present in all plants and many animals, where its function is largely unknown. It is possible that PPAL could participate in prenylation processes since it shares similarity to the α subunits of known prenylation enzymes. Prenylation is a post-translational modification of proteins that involves the addition of a lipid moiety to proteins to facilitate membrane targeting and association and promote protein-protein interactions. Prenylation has important roles in plant growth and development, including …

Computational Approaches To Understand Chemoresistance & Tumor Evolution Using Longitudinal Clinical Data And Lineage Tracing, Sahil Seth

Dissertations & Theses (Open Access)

Tumors are highly heterogeneous and dynamic, continually adapting and evolving in response to their microenvironment as well as external perturbations. Multi-region (spatial) and single cell sequencing has enabled us to anatomize the heterogeneity further and provide evidence of its association with chemo and drug resistance. To investigate this further we took two different approaches to understand the chemo-resistance, and functional heterogeneity in Triple negative breast cancer (TNBC) and Pancreatic ductal carcinoma in situ (PDAC) from an evolutionary perspective.

The first approach was to leverage tumor profiling from an ongoing randomized clinical trial in triple-negative breast cancer (ARTEMIS) to assess mechanisms …

Screening For Binding Partners And Protein-Protein Interactions Of A Fungal Transcription Factor- Xdr1, Nishadi Punsara Gallala Gamage

Masters Theses

Clarireedia spp. (formerly Sclerotinia homoeocarpaF.T. Bennett) is the causal agent dollar spot, the most economically important turfgrass disease impacting golf courses in North America. The most effective strategy for dollar spot control is repeated application of multiple classes of fungicides. However, reliance on chemical application has led to resistance to four classes of fungicides as well as multidrug resistance (MDR). Fungi are known to detoxify xenobiotics, like fungicides, through transcriptional regulation of three detoxification phases: modification, conjugation and secretion. Little is known, however, of the protein-protein interactions that facilitate these pathways. Following next-generation RNA sequencing of Clarireedia spp., a …

Cpf1-Based Crispr Genome Editing In The Cyanobacterium N. Punctiforme, Soohan Woo

University of the Pacific Theses and Dissertations

CRISPR systems have been growing in their utility and their application throughout the biological field as researchers continue to grow in their understanding of the relatively novel genome editing technology. However, despite the potential of CRISPR as a genome editing tool, the complexity of applying this technology to a specific organism calls for custom modifications to the system to improve its success rate. In this project, a CRISPR-Cpf1 system that can be effectively employed in the cyanobacterium Nostoc punctiforme was designed, with a focus on the hormogonium development of this species. Multiple plasmids containing the CRISPR system and targeting different …

Getting To The Root Cause: The Genetic Underpinnings Of Root System Architecture And Rhizodeposition In Sorghum, Farren Smith

Graduate Theses, Dissertations, and Problem Reports

Plants are some of the most diverse organisms on earth, consisting of more than 350,000 different species. To understand the underlying processes that contributed to plant diversification, it is fundamental to identify the genetic and genomic components that facilitated various adaptations over evolutionary history. Most studies to date have focused on the underlying controls of above-ground traits such as grain and vegetation; however, little is known about the “hidden half” of plants. Root systems comprise half of the total plant structure and provide vital functions such as anchorage, resource acquisition, and storage of energy reserves. The execution of these key …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Assesment Of Antibiotic Resistant Gene Expression In Clinical Isolates Of Pseudomonas Aeruginosa, Dustin Esmond

Biology Theses

Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase …

Understanding Potassium Toxicity Stress Responses Of The Extremophyte Schrenkiella Parvula Using Systems Biology Approaches, Pramod Pantha

LSU Doctoral Dissertations

Schrenkiella parvula is an extremophyte model closely related to Arabidopsis thaliana and Brassica crops. Its natural habitat includes shores of saline lakes in the Irano-Turanian region. It has adapted to grow in soils rich in multiple salts including Na⁺ and K⁺. I have investigated the genetic basis for high K⁺ tolerance in plants using S. parvula as a stress tolerant model compared to the premier plant model, Arabidopsis thaliana which is highly sensitive to salt stresses using physiological, ionomic, transcriptomic, and metabolomic approaches. Under high K⁺ stress, root system architecture changes significantly compared to control …

The Impact Of A Lynch Syndrome Diagnosis By Population Genomic Screening On Family Communication, Medical Management, And Lifestyle Changes, Reem Ibrahim Bux, Brooke Nicole Delehoy

Human Genetics Theses

The purpose of population genomic screening programs is to help in prevention and treatment of conditions that takes into account an individual’s unique genetics, environmental, and lifestyle factors. Through this “genome-first” approach, individuals at increased lifetime risk for certain conditions are identified, allowing them and their relatives to qualify for preventative medical care and surveillance (Schwartz et al., 2018). An example institution that utilizes this approach is Geisinger’s MyCode Community Initiative, where their goal is to “make healthcare better” through research and its application to patient care (MyCode Community Health Initiative, n.d.). MyCode reports back medically actionable results for conditions …

Involvement Of The Ino80 Chromatin Remodeling Complex In Cell Division And Genomic Stability, Ethan Chen

Biomedical Engineering Undergraduate Honors Theses

Cell division is a vital biological process for growth and development in both single and multi-cellular organisms—whereby the cell must duplicate its organelles and genome in entirety and appropriately distribute the copied contents to the daughter cells. Cells undergo a cycle of two distinct phases: interphase and mitosis. During interphase, the cell replicates its genomic DNA (in the form of chromosomes) located within the nucleus. DNA replication is carried out in a euchromatin state, where the chromosome structure is loose and easily accessible by DNA polymerase and other replication enzymes. Upon the completion of replication, chromatin is condensed into highly …

Initial And Advanced Stages Of Microbiota Establishment Within The Tsetse Fly, Miguel Eduardo Medina Munoz

Graduate Theses, Dissertations, and Problem Reports

Symbiosis is a long-term physical association between two or more species, although little is known regarding its evolutionary origins, particularly at the genetic level. Tsetse flies are the vector of African trypanosomes, causative agents of Human and Animal African Trypanosomiases. Tsetse provide an ideal model for studying initial and advanced stages of symbiosis. Tsetse have a simple digestive tract microbiota primarily consisting of two bacteria; the ancient mutualist Wigglesworthia glossinidia and the recently acquired Sodalis glossinidius. This work presents a chronological study in evolutionary terms of the history of a microbial-insect association. First, I present concepts on symbiosis and …

Composition And Homology In The Taxonomic Classification Of Escherichia Coli, Tanya Irani

Theses and Dissertations (Comprehensive)

As new techniques have been introduced, specifically the possibility of complete genome sequencing, better methods of defining bacterial species have also been proposed. One of the most recently proposed methods, using bioinformatic techniques, is to calculate the average nucleotide identity (ANI) between the homologous genome segments of different isolates. Another method for species discrimination that has been tested successfully is the similarity of DNA compositional signatures. However, in a recent update, DNA signatures split the available Escherichia coli complete genomes into three groups. To check if this result was consistent with such genomes belonging to different species, we tested methods …

A Cophylogenetic Analysis Of Fungus Gardening Ants And Their Symbiotic Fungi, Katherine Beigel

Biology Theses

Fungus-growing ants (Tribe Attini) and their fungal cultivars share a 50-million-year coevolutionary history. Large scale phylogenetic analyses depict a strong co-phyletic signal among ants and their farmed fungi yet fungus sharing among unrelated ant lineages is somewhat widespread. An overview of sharing has been hampered by a lack of genetic markers that exhibit intraspecific variation and surveys across geographic regions. For example, previous studies have shown similar sequences of the internal transcribed spacer (ITS) region of fungus in different species of Trachymyrmex, suggesting that these ant species are farming the same fungal clone. To examine whether this was a …

The Effect Of Nuclear Perturbations On The 3d Organization Of The Genome, Rosela Golloshi

Doctoral Dissertations

Cells in our body experience constant mechanical forces that influence biological functions such as growth and development. The nucleus has been implicated as a key mechanosensor and can directly influence chromatin organization and epigenetic alterations leading to gene expression changes. However, the mechanism by which such mechanical forces lead to genomic alterations and expression of mechanosensitive genes is not fully understood. The work presented in this dissertation investigates the effect of mechanical and epigenetic perturbations on the 3D genome organization. To investigate this 3D genome folding, we use Chromosome Conformation Capture followed by high throughput sequencing (Hi-C) (Chapter-1) which identifies …

Quantifying Structure And Variation In Complex Phylogenetic Data, Genevieve Geraldine Mount

LSU Doctoral Dissertations

Identifying the source and structure of variation in nature is crucial to understanding fundamental aspects of evolution. Despite a recent plethora of genetic and morphological data, many interesting questions about the relationships between different groups remain unresolved. My dissertation evaluates three approaches for identifying and quantifying the variation within phylogenetic datasets. Characterizing variation within datasets and across analytical methods gives insight into biologically interesting characters, unusual evolutionary processes, and areas for model improvement.

Network-based community detection approaches offer a powerful tool to describe variation in phylogenetic signal across the genome (i.e., gene tree variation). In Chapter 2, I investigate the …

Structure And Evolution Of Lizard Immunity Genes, Trent Santonastaso

University of New Orleans Theses and Dissertations

One of the most important gene families to play a role in adaptive immunity is the major histocompatibility complex (MHC). MHC class II loci are considered to be the most variable loci in the vertebrate genome, and studies have shown that this variability can be maintained through complex co-evolutionary dynamics between host and parasite. Despite the rich body of research into the MHC, there is comparatively little understanding of its genomic architecture in reptiles. Similarly, loci associated with innate immunity have received little attention in reptiles compared to other vertebrates. In the first chapter, we investigated the structure and organization …

A Genomic Analysis Of Bobcat Populations In North America With A Comparison To The Canada Lynx: An Assessment Of Local Adaptation To Unique Ecoregions And Phylogeography, Jennifer C. Broderick

Electronic Theses and Dissertations

Bobcats (Lynx rufus) are an ecologically and genetically diverse species with a large contiguous range throughout North America. The species not only has a wide array of phenotypic variation compared to other mammals, but shows marked adaptability across ecozones with differing ecological influences. It is these various selective pressures in distinctive parts of the continent that have likely led to localized adaptations within the bobcat metapopulations. The species is also marked by its ability to maintain connectivity and populations in anthropogenically developed areas, an advantage it has over other felids, including its close relative the Canada lynx ( …

Evolutionary Ecology Of Host-Parasite Relationships: Role Of Host Ecology, Phylogeny, And Demographics In Shaping Parasite Evolution, Erika Taylor Gendron

Biology ETDs

Host-parasite systems exist across complex and ecologically heterogeneous landscapes, and may occur across taxonomically and ecologically disparate host species. Under these conditions, mechanisms underlying microevolutionary processes (i.e. gene flow, genetic drift) are not always clear, and may be mediated by numerous co-occurring factors specific to individual hosts. Host traits such as host immunology, demographics, phylogeny and ecology may act in concert to shape host-parasite relationships, and ultimately evolutionary processes. The research described herein used phylogeographic, phylogenomic, and population genetic methods to further understanding of how host traits impact the evolutionary ecology of trematode systems, using avian schistosomes (Digenea: Schistosomatidae) as …

De-Coding The Impact Of Evolved Changes In Gene Expression And Cellular Phenotype On Primate Evolution, Trisha Zintel

Doctoral Dissertations

The goal of the dissertation work outlined here was to investigate the influence of proximal processes contributing to evolutionary differences in phenotypes among primate species. There are numerous previous comparative analyses of gene expression between primate brain regions. However, primate brain tissue samples are relatively rare, and my results have contributed to the pre-existing data on more well-studied primates (i.e. humans, chimpanzees, macaques, marmosets) as well as produced information on more rarely-studied primates (i.e. patas monkey, siamang, spider monkey). Additionally, the primary visual cortex has not previously been as extensively studied at the level of gene expression as other brain …

Interspecific Gene Flow Potentiates Adaptive Evolution In A Hybrid Zone Formed Between Pinus Strobiformis And Pinus Flexilis, Mitra Menon

Theses and Dissertations

Species range margins are often characterised by high degrees of habitat fragmentation resulting in low genetic diversity and higher gene flow from populations at the core of the species range. Interspecific gene flow from a closely related species with abutting range margins can increase standing genetic diversity and generate novel allelic combinations thereby alleviating limits to adaptive evolution in range margin populations. Hybridization driven interspecific gene flow has played a key role in the demographic history of several conifer due to their life history characteristics such as weak crossability barriers and long generation times. Nevertheless, demonstrating whether introgression is adaptive …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …