Biology Commons^™

Genetic Imputation: Accuracy To Application, Shelina Raynell Ramnarine

Arts & Sciences Graduate Student Theses and Dissertations

Genotype imputation, the process of inferring genotypes for untyped variants, is used to identify and refine genetic association findings. This body of work focuses on assessing imputation accuracy and uses imputed data to identify genetic contributors to mentholated cigarette preference. Inaccuracies in imputed data can distort the observed association between variants and a disease. Many statistics are used to assess accuracy; some compare imputed to genotyped data and others are calculated without reference to true genotypes. Prior work has shown that the Imputation Quality Score (IQS), which is based on Cohens kappa statistic and compares imputed genotype probabilities to true …

Metal Selectivity And Acquisition By The Yersiniabactin Metallophore System In Escherichia Coli, Eun-Ik Koh

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTI) are one of the most common bacterial infections, of which, the majority are caused by uropathogenic Escherichia coli (UPEC). Many bacterial pathogens including UPEC synthesize and secrete chemically diverse metabolites called siderophores, which are classically defined by their ability of bind and deliver iron(III), an essential nutrient, to pathogens during infections. UPEC isolates can express multiple siderophore systems, of which, the virulence-associated siderophore yersiniabactin (Ybt) binds to both iron(III) and copper(II) during urinary tract infections. In this thesis we show that Ybt interacts with multiple physiologic transition metals and acts as a metallophore system to deliver …

The Resolution Phase Of Nk Cell Proliferation And Ifn Production Following Viral Infection Are Highly Regulated Processes., Leslie Abigail Fogel

Arts & Sciences Graduate Student Theses and Dissertations

In response to MCMV infection, NK cells undergo three distinct phases of proliferation: the non-specific phase mediated by pro-proliferative cytokines; the specific phase mediated by recognition of an MCMV-encoded protein by an NK cell activating receptor, Ly49H; and the resolution phase, whose mechanism is unknown. MCMV infection of RAG mice, which lack all adaptive immune cells, results in prolonged proliferation of NK cells despite similar viral titers compared to wildtype mice. Interestingly, there are different kinetics for Ly49H+ and Ly49H- NK cells. We have identified several additional markers that may distinguish NK cells that have been specifically activated through their …

Structure And Dynamics Of A Small Multidrug Resistance Transporter, Emre, Chao Wu

Arts & Sciences Graduate Student Theses and Dissertations

EmrE is a small multidrug resistance transporter in E. coli. It effluxes a wide range of antibiotics, thus contributing to the evolving epidemic of drug resistance. Despite its small size, EmrE is a fully functional transporter making it an ideal model system for a comprehensive study of the multidrug transport mechanism. In the transport cycle, EmrE must alternate between outward- and inward-facing conformations upon substrate binding to translocate substrates across the membrane. High-resolution structures of EmrE in complex with substrates facing different sides of the membrane will shed light on the coupling mechanism between substrate binding and transport. However, the …

Role Of Atg16l1 In Uropathogenic E. Coli Pathogenesis, Jane Symington

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are among the most common infectious diseases and are primarily caused by uropathogenic E. coli (UPEC). Given the greater incidence of antibiotic resistance among UPEC isolates, it is vital to determine factors and pathways important for an effective host response to UPEC in order to improve therapeutic options for combating UTIs. Autophagy is a cellular degradation pathway that plays important roles in pathogen control and modulation of innate immunity. One essential autophagy protein, ATG16L1, has been further implicated in controlling inflammation due to a common variant of ATG16L1 being associated with increased risk of Crohns disease, …

Development And Application Of Comparative Gene Co-Expression Network Methods In Brachypodium Distachyon, Henry David Priest

Arts & Sciences Graduate Student Theses and Dissertations

Gene discovery and characterization is a long and labor-intensive process. Gene co-expression network analysis is a long-standing powerful approach that can strongly enrich signals within gene expression datasets to predict genes critical for many cellular functions. Leveraging this approach with a large number of transcriptome datasets does not yield a concomitant increase in network granularity. Independently generated datasets that describe gene expression in various tissues, developmental stages, times of day, and environments can carry conflicting co-expression signals. The gene expression responses of the model C3 grass Brachypodium distachyon to abiotic stress is characterized by a co-expression-based analysis, identifying 22 modules …

The Molecular And Cellular Basis For Cold Sensation, Daniel Brenner

Arts & Sciences Graduate Student Theses and Dissertations

The ability to sense changes in temperature is crucial to surviving harsh environments. Over the last decade several ion channels that have been proposed to be cold sensitive have been identified, most notably TRPM8 and TRPA1. Although these molecules have been extensively studied in vitro, their exact roles in cold sensation in vivo are still debated. This uncertainty is in large part due to problems with the standard methods of testing cold sensitivity in vivo, which often rely on subjective measures of cold responsiveness. Experiments using these subjective measures have been repeated by different groups and have yielded conflicting results, …

Modulation Of Human And Malarial Glucose Transporter Activity By Lipids And Small Molecules, Thomas E. Kraft

Arts & Sciences Graduate Student Theses and Dissertations

Glucose transport is a fundamentally important process for maintenance and regulation of cellular metabolism in all kingdoms of life. Despite their high importance, detailed examination of glucose transport proteins in humans and parasites through biochemical, biophysical and structural properties was greatly hampered by the inability to express, purify and reconstitute sufficient amounts of active transporters. This dissertation describes strategies that led to the first successful expression, purification, stabilization and functional reconstitution of active insulin-responsive GLUT4 transport protein. Furthermore, the work described herein establishes a requirement of anionic and conical lipids for full activity of the mammalian glucose transporters GLUT3 and …

Regulation Of Epithelial Turnover By Host-Virome Interactions, Lulu Sun

Arts & Sciences Graduate Student Theses and Dissertations

The host immune system must constantly function to maintain chronic commensal and pathogenic organisms in check. These organisms include the virome, which is the viral component of the microbiome. The consequences of immune responses to the virome on host physiology are as yet unexplored, and may have long-term implications in health and disease. Here, I used both genetic and infectious mouse models to investigate how the innate antiviral cytokines Type I interferons (IFNs) modulate epithelial turnover. I first found that mice deficient in Irgm1, a p47 GTPase, had persistently elevated Type I IFNs even in the absence of exogenous viral …

Iron Regulation Of Macrophage Responses To Uropathogenic E. Coli, Nana Kwame Owusu-Boaitey

Arts & Sciences Graduate Student Theses and Dissertations

Uropathogenic E. coli (UPEC) are the principal cause of urinary tract infections (UTIs), one of the most common infections globally. Given the rising incidence of antibiotic resistance among UPEC strains, there is an increasing need to better understand the host response to UPEC and to develop ways to harness the bladder innate immune response that clears infection. In response to infection, the host attempts to limit the ability of UPEC to access iron, a metal critical to UPEC survival. Innate immune cells known as macrophages are known to regulate iron homeostasis through the production of pro-inflammatory cytokines, though it remains …

Omcp Mediated Cowpox Virulence And Its Dependence On The Immune Receptors Nkg2d And Fcrl5., Michel Muzi Sun

Arts & Sciences Graduate Student Theses and Dissertations

Viruses with large DNA genomes, such as cowpox virus, encode many open-reading frames involved in the modulation of the host immune system, facilitating escape from immune detection or downregulation of specific aspects of the host immune response. Investigation of virally-encoded immunoevasins has been instrumental in understanding host-pathogen interactions. Here, we focus on the cowpox virus immunoevasin Orthopoxvirus MHC Class I-like Protein (OMCP) and demonstrate for the first time that OMCP facilitates cowpox virus virulence in vivo. We have previously documented that OMCP binds the activating receptor NKG2D on NK cells as well as the orphan receptor FCRL5 on innate B …

Superoxide Dismutase 1: Novel Insights On Disease Models And Tissue Specificity In Amyotrophic Lateral Sclerosis, Matthew James Crisp

Arts & Sciences Graduate Student Theses and Dissertations

Mutations in superoxide dismutase 1 (SOD1) are known to cause dominantly-inherited amyotrophic lateral sclerosis (ALS), a rapidly-fatal adult-onset neurodegenerative disorder defined by motor neuron loss and progressive paralysis. In the past twenty years, research into the disorder has been driven by the creation of numerous transgenic animal models that have yielded multiple theories on the pathogenesis of the disease. Patients and animal models with SOD1 mutations express the defective protein in every cell, yet the disease only affects tissues in the neuromuscular axis. In this dissertation, I present original work exploring two aspects of SOD1 ALS. The first details the …

The Role Of Dnmt3a In Acute Myeloid Leukemia Pathogenesis, Christopher Browning Cole

Arts & Sciences Graduate Student Theses and Dissertations

Loss of function mutations in the DNA methyltransferase DNMT3A are highly recurrent in acute myeloid leukemia (AML). DNMT3A and the highly homologous gene DNMT3B encode the two methyltransferases that are primarily responsible for mediating de novo methylation of specific DNA sequences during cellular differentiation. DNMT3A mutations are mutually exclusive of several translocations that create oncogenic fusion genes (PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, and MLL-X), suggesting that these fusions may require functional DNMT3A to initiate leukemogenesis. Using bone marrow cells from a constitutive Dnmt3a null mouse, we show that loss of Dnmt3a caused a striking loss of DNA methylation throughout the genome of …

Understanding The Interactions Of Developing Thymocytes And Antigen Presenting Cells In The Thymic Medulla, Justin Shaun Arnold Perry

Arts & Sciences Graduate Student Theses and Dissertations

Various thymic APC subsets have been invoked in deletional tolerance and Treg cell induction, but previous studies either assessed total T cell numbers or used TCR transgenic lines, obscuring roles that individual thymic APC subsets might serve for particular antigen-specific T cell populations. Utilizing T cell receptor sequencing, we found that medullary thymic epithelial cells (mTECs) and bone marrow-derived (BM) APCs delete or select unique conventional and Treg cell TCR repertoires, demonstrating distinct roles for these APCs. We show that BM APCs and mTECs each contribute to Aire-dependent T cell tolerance development, albeit through either cooperative or autologous antigen presentation …

Refining Associations Between Targeted Genes And The Development Of Substance Use Disorders, Emily Olfson

Arts & Sciences Graduate Student Theses and Dissertations

Recent genome-wide association studies (GWAS) provide strong evidence for the contribution of a few specific genes to alcohol and nicotine dependence. Chapter 2 explores numerous previously identified candidate genes for alcohol dependence using a publicly available GWAS. I found that many candidate loci do not replicate, highlighting the utility of GWAS for focusing on disease associated genes. Chapters 3-5 dissect associations between three genome-wide significant genes and substance use disorders. Chapter 3 focuses on a functional variant in alcohol dehydrogenase (ADH) 1B. Through examining 1,550 adolescent drinkers in the Collaborative Study on the Genetics of Alcoholism (COGA), I extended adult …

Application Of Genomic Technologies To Study Infertility, Nicholas Rui Yuan Ho

Arts & Sciences Graduate Student Theses and Dissertations

An estimated one in eight couples in the United States are diagnosed with infertility. There is a significant genetic contribution to infertility, with estimates of heritability ranging from 0.2 to 0.5. We know surprisingly little about the genetic causes, with only slightly more than a hundred genes known to cause human infertility. I have been translating recent advances in genomics to study infertility in a more efficient manner, in order to improve our knowledge of the genetic causes. By using high throughput genomics and proteomics datasets from other groups, I was able to feed that into a machine learning algorithm …

Granulocyte-Colony Stimulating Factor Reprograms The Bone Marrow Microenvironment To Suppress B Lymphopoiesis, Ryan Brent Day

Arts & Sciences Graduate Student Theses and Dissertations

The production of hematopoietic cells in the bone marrow is tightly and dynamically regulated in response to environmental stimuli. In response to infection, the bone marrow increases granulopoiesis at the expense of lymphopoiesis. The mechanisms mediating this shift are poorly understood. We show that treatment with granulocyte-colony stimulating factor (G-CSF), which is often induced during infection, results in marked decline of B lymphocytes at multiple stages of bone marrow B cell development. Transgenic mouse models show that G-CSF acts in a non-cell intrinsic fashion through cells of the monocyte-macrophage lineage to suppress B lymphopoiesis by downregulating important B trophic factors …

A Novel Ultrashort Pulsed Laser Method For Pathogen Inactivation, Shaw-Wei David Tsen

Arts & Sciences Graduate Student Theses and Dissertations

Emerging viral pathogens represent a constant and prominent threat to human health worldwide. There is a dire need to develop new pathogen inactivation techniques that can be used to safeguard the blood supply and to generate inactivated vaccines against these emerging viruses. Unfortunately, current techniques are inadequate because they introduce toxic/carcinogenic chemicals or alter the structure of the products, leading to loss of safety and efficacy. We have developed a novel, chemical-free ultrashort pulsed laser treatment system capable of inactivating a broad spectrum of both enveloped and non-enveloped viruses. We found that ultrashort pulsed laser treatment targets the vibrational modes …

Mechanism Of Calcium-Dependent Chloride Channel Activation By The Secreted Regulator Clca1, Zeynep Yurtsever

Arts & Sciences Graduate Student Theses and Dissertations

The calcium-activated chloride channel regulator (CLCA) proteins are key signaling molecules, which are implicated in various diseases through their tissue-specific expression. Human CLCA1 protein, overexpressed in airway epithelia under pathophysiological conditions, is centrally involved in the manifestation of IL-13-driven mucus cell metaplasia (MCM), a hallmark feature of asthma and chronic obstructive pulmonary disease (COPD), for which there are currently no available therapeutics. Elucidating the poorly understood molecular basis of CLCA1 function is thus required to design specific inhibitors of CLCA1 activity to treat MCM in asthma and COPD. Originally misannotated as ion channels, CLCA proteins are secreted soluble proteins that …

The Murine Accessory Olfactory Bulb As A Model Chemosensory System: Experimental And Computational Analysis Of Chemosensory Representations, Gary Francis Hammen

Arts & Sciences Graduate Student Theses and Dissertations

A common challenge across sensory processing modalities is forming meaningful associations between the neural responses and the outside world. These neural representations of the world must then be integrated across different sensory systems contributing to each individuals perceptual experience. While there has been considerable study of sensory representations in the visual system of humans and multiple model organisms, other sensory domains, including olfaction, are less well understood. In this thesis, I set out to better understand the sensory representations of the mouse accessory olfactory system (AOS), a part of the olfactory system. The mouse AOS, our model chemosensory system, comprises …

Impacts From The Use Of Antibiotics In Livestock: Methods Of Transmission Of Antibiotic Resistance From Livestock To Humans, Kristin M. Walden

Biology: Student Scholarship & Creative Works

Antibiotic use in livestock production has been around since the 1950s. Antibiotic feed is used in livestock and other meat producing animals for three reasons: illness prevention, illness treatment, and growth promotion. Unfortunately, since the time that antibiotics were first invented, antibiotic resistant bacteria have become a threat to public health. There are many studies showing methods of transmission of antibiotic resistance from livestock to humans. Antibiotic resistance can spread from livestock to soil, water, insects, and food, which ultimately comes into contact with humans. A proposed study to measure antibiotic resistance when eliminating antibiotic feed will provide a hypothesis …

Postembryonic Polarity Modification In The Acoel Convolutriloba Longifissura, Eric Young, James M. Sikes Ph.D.

Undergraduate Honors Theses

Metazoans establish the bilateral body plan early in embryogenesis by patterning orthogonal body axes with polarity that is unaltered during the lifetime of most animals. While some organisms re-establish/modify body axes during regeneration and asexual reproduction, the acoel flatworm Convolutriloba longifissura is unusual in its ability to modify left-right (L-R) axis polarity during longitudinal fission. We have developed C. longifissura as a model for studying the mechanisms of L-R polarity modification during postembryonic development. Regeneration experiments have elucidated the temporal dynamics of midline re-specification, suggesting that parallel L-R axes replace the pre-existing midline prior to longitudinal fission. We have characterized …

Successful Enrichment And Recovery Of Whole Mitochondrial Genomes From Ancient Human Dental Calculus, Andrew T. Ozga, Maria A. Nieves-Colon, Tanvi P. Honap, Krithivasan Sankaranarayanan, Courtney A. Hofman, George R. Milner, Cecil M. Lewis Jr., Anne C. Stone, Christina Warinner

Biology Faculty Articles

Objectives

Archaeological dental calculus is a rich source of host‐associated biomolecules. Importantly, however, dental calculus is more accurately described as a calcified microbial biofilm than a host tissue. As such, concerns regarding destructive analysis of human remains may not apply as strongly to dental calculus, opening the possibility of obtaining human health and ancestry information from dental calculus in cases where destructive analysis of conventional skeletal remains is not permitted. Here we investigate the preservation of human mitochondrial DNA (mtDNA) in archaeological dental calculus and its potential for full mitochondrial genome (mitogenome) reconstruction in maternal lineage ancestry analysis.

Materials and …

Determining The Pollination Mechanism Of A Problematic Invasive Species In The Gulf South: Triadica Sebifera, Jennifer Wester Clark

LSU New Orleans Theses and Dissertations

Understanding the ecology of invasive species is vital to curb the homogenizing of ecosystems, yet the pollination mechanisms of the Chinese tallow tree (Triadica sebifera) in its introduced habitat remain ambiguous. This study examines self-pollination, wind pollination, and flower-visiting insects of tallow in a bottomland hardwood forest and Longleaf pine savannah in the U.S. Gulf South. These data suggest that self-pollination and airborne pollination are possible, but likely rare occurrences, although the possibility of apoxisis was not investigated. Seed production in exclusion experiments was significantly less than in open-pollinated flowers, and wind dispersal of tallow pollen dropped to …

A Novel Variant In Cmah Is Associated With Blood Type Ab In Ragdoll Cats, Barbara Gandolfi, Robert Grahn, Nicholas Gustafson, Daniela Proverbio, Eva Spada, Badri Adhikari, Janling Cheng, Gordon Andrews, Leslie Lyons, Chris Helps

Computer Science Faculty Works

The enzyme cytidine monophospho-N-acetylneuraminic acid hydroxylase is associated with the production of sialic acids on cat red blood cells. The cat has one major blood group with three serotypes; the most common blood type A being dominant to type B. A third rare blood type is known as AB and has an unclear mode of inheritance. Cat blood type antigens are defined, with N-glycolylneuraminic acid being associated with type A and N-acetylneuraminic acid with type B. Blood type AB is serologically characterized by agglutination using typing reagents directed against both A and B epitopes. While a genetic characterization of blood …

The Gowanus Canal: Delving Into The Murky And Mysterious Waters Of Brooklyn’S Toxic Canal, Victoria L. Von Ancken

Student Theses 2015-Present

Like many environmental issues we face today, the Gowanus Canal began as a hopeful tale. It was envisioned as a promising cargo transportation waterway in Brooklyn, New York. However, due to reckless planning with little thought for the future, the canal slowly began to have a negative effect on its surrounding landscape and community, as well as abandoning its initial purpose, and ultimately sitting stagnant in the neighborhood. Today, the canal is a large environmental problem we face and is in great need of cleanup. The canal is a prime example of a lack of planning and consequential detrimental effects …

Ocean Acidification And Predator-Prey Relations: Correlating Disruption Of Predator Avoidance With Chemosensory Deficits, Alexandra Fw Sidun, William G. Wright

Student Scholar Symposium Abstracts and Posters

One of the most destructive effects of global climate change is the increased carbon sequestering and consequential acidification of our world’s oceans. The impacts of ocean acidification on marine organisms are still relatively unknown, especially effects on behavioral ecology. Avoiding predation has emerged from recent behavioral ecology literature as a critical feature in the life history of a wide array of animal species; experiments on marine fishes suggest acidic water compromises their predator-avoidance abilities. Recent assays in our lab suggest predator-induced behavior is reduced by weakly acidic water. These experiments do not address the potential factor of generalized malaise caused …

Connecting The Physiological And Behavioral Response To Heat Stress On A Warming Planet, Anastasia Kalyta

Student Scholar Symposium Abstracts and Posters

Intertidal communities are considered good models of the biological effects of climate change on ecosystems, as their resident organisms are subjected to heat spells during daytime low tides. The increasing heat exposure can elicit behavioral as well as physiological responses in intertidal organisms. We studied the relationship between these responses to heat stress in the blue-banded hermit crab, Pagurus samuelis, by inducing a “heat shock” with elevated water temperature of 29 °C for 2.5 h. The behavioral effect of heat-shock was quantified using a 30-minute feeding assay, measuring the mass of a standard squid pellet consumed by individual hermit crabs. …

Destruction Of Opportunistic Pathogens Via Polymer Nanoparticle-Mediated Release Of Plant-Based Antimicrobial Payloads, Dahlia N. Amato, Douglas V. Amato, Olga V. Mavrodi, Dwaine A. Braasch, Susan E. Walley, Jessica R. Douglas, Dmitri V. Mavrodi, Derek L. Patton

Faculty Publications

The synthesis of antimicrobial thymol/carvacrol‐loaded polythioether nanoparticles (NPs) via a one‐pot, solvent‐free miniemulsion thiol‐ene photopolymerization process is reported. The active antimicrobial agents, thymol and carvacrol, are employed as “solvents” for the thiol‐ene monomer phase in the miniemulsion to enable facile high capacity loading (≈50% w/w), excellent encapsulation efficiencies (>95%), and elimination of all postpolymerization purification processes. The NPs serve as high capacity reservoirs for slow‐release and delivery of thymol/carvacrol‐combination payloads that exhibit inhibitory and bactericidal activity (>99.9% kill efficiency at 24 h) against gram‐positive and gram‐negative bacteria, including both saprophytic (Bacillus subtilis ATCC 6633 and Escherichia coli …

Discrete But Variable Structure Of Animal Societies Leads To The False Perception Of A Social Continuum, Dustin R. Rubenstein, Carlos A. Botero, Eileen A. Lacey

Biology Faculty Research

Animal societies are typically divided into those in which reproduction within a group is monopolized by a single female versus those in which it is shared among multiple females. It remains controversial, however, whether these two forms of social structure represent distinct evolutionary outcomes or endpoints along a continuum of reproductive options. To address this issue and to determine whether vertebrates and insects exhibit the same patterns of variation in social structure, we examined the demographic and reproductive structures of 293 species of wasps, ants, birds and mammals. Using phylogenetically informed comparative analyses, we found strong evidence indicating that not …