Biology Commons^™

Ecological And Genetic Consequences Of Climate Change Impacting Species Distributions, With Specific Cases In Whitebark Pine (Pinus Albicaulis Engelm.), Jennifer A. Gruhn

Arts & Sciences Graduate Student Theses and Dissertations

Climate is widely recognized as a primary factor contributing to species distribution limits. In turn, species’ geographic ranges have contracted and expanded in concert with Earth’s climatic history and are predicted to shift in response to future climate change. We investigated the ecological and genetic consequences of species distributions in flux with their historical, current, and projected future climatic environments. Chapter 1 introduces themes and background information related to the thesis research found in Chapters 2 through 4. In Chapter 2, we questioned the extent to which ancestral climate-related traits are conserved through vast periods of evolutionary time spanning the …

The P38mapk-Mk2-Hsp27 Axis Regulates The Mrna Stability Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Hayley Reynolds Moore

Arts & Sciences Graduate Student Theses and Dissertations

Protecting the genome is a vital aspect of safeguarding organismal health. Inability to efficiently and effectively replicate the genome or repair damage the genome may encounter can lead to mutational accumulation or senescence, both of which are drivers of multiple diseases including cancer. Understanding the mechanisms by which the genome is maintained, as well as the consequences of repeated rounds of replication or exposure to DNA damaging agents, will allow for greater understanding of the diseases they promote as well as development of targeted therapies aimed at mitigating the detrimental effects of genomic insult. The first section of my work …

Population Structure And Mating Dynamics In The Social Amoeba Dictyostelium Discoideum, Tracy Edwards Douglas

Arts & Sciences Graduate Student Theses and Dissertations

Successfully investigating the evolution and maintenance of sex and mating systems can often have as much to do with choosing the right study system as it has to do with asking the right questions. Dictyostelium discoideum has long been the focus of researchers interested in understanding a number of biological processes, such as motility, chemotaxis and development. More recently, attentions have shifted to include questions about the evolution of social and sexual interactions both within and between species. The D. discoideum life cycles, both asexual and sexual, are uniquely social, each requiring a costly sacrificial act. This offers an ideal …

Action Of Snail1 Protein Is Critical For Fibrosis, Hirak Biswas

Arts & Sciences Graduate Student Theses and Dissertations

Hypoxic injury to the heart causes cardiac fibrosis leading to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor which has been implicated in fibrosis following organ injury. To investigate the role of SNAIL1 in cardiac fibrosis, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 is expressed in the infarcted myocardium, especially in the myofibroblasts. Utilizing cardiac fibroblasts in-vitro we demonstrate that pro-fibrotic factors and collagen increases SNAIL1 in cardiac fibroblasts. By knocking out SNAIL1 in cardiac fibroblasts in-vitro, we demonstrate that SNAIL1 is required for adoption …

Differential Associations Of Stress And Cortisol With Brain Structure And Cognition In Cognitively Normal Older Adults, Ana Kim

Arts & Sciences Graduate Student Theses and Dissertations

The current literature shows discrepant findings as to the degree to which cumulative stress and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis are associated with brain structure and cognitive function in older adults, particularly in brain regions with high expression of receptors for glucocorticoid, and cognitive function reliant upon these regions. Past studies have been heavily focused on total hippocampus while limited studies have examined hippocampal subdivisions or other brain structures. In addition, one key moderator that may influence the associations of cumulative stress and cortisol on brain structure and cognition is the single-nucleotide polymorphisms (SNPs) of the stress-system genes, which …

Investigating Auxin Biosynthesis And Its Contribution To Virulence By Pseudomonas Syringae Pv Tomato Dc3000, Sheri Mcclerklin

Arts & Sciences Graduate Student Theses and Dissertations

Auxin is a major hormone that regulates many processes in plant development and has been shown to be important in several plant-pathogen interactions. Many microbes, including multiple pathovars of Pseudomonas syringae produce indole-3-aceitc acid (IAA), a naturally occurring auxin. However IAA production and its biosynthesis pathway remains undetermined for many bacteria including P. syringae strain DC3000, the subject of this thesis. To investigate IAA biosynthesis by DC3000, I examined IAA production in cultures fed with different pathway intermediates. I show that DC3000 produces IAA in culture and cultures supplemented with Indole-3-acetaldehyde (IAAld) produced high levels of IAA, indicating that IAAld …

Regulation Of Transcription And Stress Response By Card In Mycobacteria, Ashley Louise Garner

Arts & Sciences Graduate Student Theses and Dissertations

Mycobacterium tuberculosis, the causative agent of Tuberculosis, infects over one third of the world's population. To control this epidemic, we must develop new chemotherapeutic strategies for treatment, which requires further insight into the physiology of this bacterium. Previous studies have identified CarD as a transcriptional regulator essential during both acute and persistent infection. Depletion of CarD sensitizes strains to a diverse panel of stresses and deregulates several hundred genes and ribosomal RNA (rRNA) which suggested that CarD may be a transcriptional regulator. Chromatin immunoprecipitation sequencing experiments showed that CarD was localized to promoters throughout the genome, suggesting that CarD regulates …

The Role Of Epidermal Enhancer 923 In The Chromatin Architecture And Transcriptional Regulation Of The Epidermal Differentiation Complex, Inez Oh

Arts & Sciences Graduate Student Theses and Dissertations

The epidermis covers the surface of the skin and provides a functional barrier across the entire body. Epidermal cells or keratinocytes proliferate in the innermost basal layer and migrate upwards into the suprabasal spinous and granular layers as they differentiate, and finally into the terminally differentiated outermost stratum corneum. Keratinocytes undergoing terminal differentiation are marked by tissue-specific concomitant expression of genes encoded in the Epidermal Differentiation Complex (EDC) locus. The EDC genes are organized into four gene families - S100, Sprr, Lce, and Flg-like, which are coordinately expressed upon activation of the terminal differentiation program in keratinocytes. The molecular mechanisms …

Mechanisms Of Extracellular Vesicle Biogenesis, Charles Eldon Jackson

Arts & Sciences Graduate Student Theses and Dissertations

Extracellular vesicles (EVs) are important mediators of intercellular communication. Different types of EVs are released from cells by either fusion of late endsomal multivesicular bodies with the plasma membrane (exosomes) or direct budding from the plasma membrane (ectosomes). Topologically equivalent processes including intralumenal vesicle formation for degradation in the endosomal pathway and virus budding from the plasma membrane depend on the ATPase VPS4 and its Endosomal Sorting Complex Required for Transport (ESCRT)-III substrates for membrane fission and release. Whether this machinery is generally required for EV biogenesis has, however, been the subject of debate. Studies of the EV proteome from …

Use Of Proteomics To Probe Dynamic Changes In Cyanobacteria, Amelia Yen Nguyen

Arts & Sciences Graduate Student Theses and Dissertations

Cyanobacteria are unicellular photosynthetic microorganisms that capture and convert light energy to chemical energy, which is the precursor for feed, fuel, and food. These oxygenic phototrophs appear blue-green in color due to the blue bilin pigments in their phycobilisomes and green chlorophyll pigments in their photosystems. They also have diverse morphologies, and thrive in terrestrial, marine water, fresh water, as well as extreme environments. Cyanobacteria have developed a number of protective mechanisms and adaptive responses that allow the photosynthetic process to operate optimally under diverse and extreme conditions. Prolonged deprivation of essential nutrients, such as nitrogen and sulfur, commonly found …

Infantile Batten Disease: Effective Therapy And Novel Model, Charles Shyng

Arts & Sciences Graduate Student Theses and Dissertations

Infantile neuronal ceroid lipofuscinosis (INCL, Infantile Batten) is typically an early onset, neurodegenerative lysosomal storage disorder. INCL is caused by mutations to the gene CLN1 which codes for the lysosomal enzyme palmitoyl-protein thioesterase-1 (PPT1). PPT1 is a soluble lysosomal enzyme that functions to cleave fatty acyl chains from proteins destined for degradation. Deficiency in PPT1 leads to the accumulation of autofluorescent storage material, a hallmark of the NCLs. The storage material has been implicated in progressive histopathological changes in the brain such as neuronal loss, astrocytosis, microgliosis, and immune cell infiltration. These histopathological changes result in a progression of clinical …

Gene Association Mapping In The Era Of Next-Generation Sequencing And Systems Biology, Tianxiao Zhang

Arts & Sciences Graduate Student Theses and Dissertations

In the past decade, advancement of genotyping technology, first microarray then “next-generation” sequencing, has enabled scientists to examine the susceptible genes that contribute to the risk of complex disorders using a genome-wide, “hypothesis free” strategy. However, despite this “hypothesis free” label, these genome-wide approaches (including genome-wide association and whole genome sequencing studies) depend on two implicit assumptions. The first assumption is that the genetic risk of complex traits is contributed by independent genes/variants (assumption of independence).The second assumption is that different genes have equal potentiality to confer to the genetic predisposition of the complex traits (assumption of equality). Despite the …

Systematics And Evolution Of The Arundinoideae And Micrairoideae (Poaceae), Jordan Kinsley Teisher

Arts & Sciences Graduate Student Theses and Dissertations

The grass family, Poaceae, is one of the most ecologically and economically important plant groups on Earth. However, the large size (over 11,000 species) and geographic range of the family makes complete resolution of the evolutionary relationships in Poaceae challenging, with some significant groups remaining neglected. Two such understudied clades, subfamilies Arundinoideae and Micrairoideae, possess an incredible amount of morphological and ecological diversity for their sizes, making them a potentially rewarding system in which to study evolution of a wide range of grass features. In this dissertation, I resolved many of the long-standing systematic issues in Arundinoideae and Micrairoideae and …

Functions Of The Dna Polymerase Delta Replicase In Lagging Strand Replication, Joseph L. Stodola

Arts & Sciences Graduate Student Theses and Dissertations

The work described in this dissertation focuses on several aspects of DNA replication in the model organism Saccharomyces cerevisiae, with particular attention paid to the function of the replicative DNA polymerase delta (Pol ), and its functions in Okazaki fragment synthesis and maturation. The first major theme of this dissertation is investigating the role that metal binding motifs play in the structure and function of Pol and other budding yeast polymerases. First, I discuss the role that two metal binding motifs within the catalytic subunit of Pol play in creating the multi-subunit polymerase complex and in promoting crucial interactions with …

Theory Of Inclusive Fitness, David C. Queller

Biology Faculty Research

A review of Social Evolution and Inclusive Fitness Theory: An Introduction. By James A. R. Marshall. Princeton (New Jersey): Princeton University Press. $39.95. xix + 195 p.; ill.; index. ISBN: 978-0-691-16156-3. 2015.

Autophagic Turnover Of Inactive 26s Proteasomes In Yeast Is Directed By The Ubiquitin Receptor Cue5 And The Hsp42 Chaperone, Richard S. Marshall, Fionn Mcloughlin, Richard D. Vierstra

Biology Faculty Research

Highlights

• The yeast 26S proteasome is degraded by Atg8-mediated autophagy
• Nitrogen starvation and inactivation stimulate proteaphagy via distinct pathways
• Proteasome inhibition is accompanied by extensive ubiquitylation of the complex
• Proteaphagy engages the Cue5 autophagy receptor and the Hsp42 chaperone

Summary

The autophagic clearance of 26S proteasomes (proteaphagy) is an important homeostatic mechanism within the ubiquitin system that modulates proteolytic capacity and eliminates damaged particles. Here, we define two proteaphagy routes in yeast that respond to either nitrogen starvation or particle inactivation. Whereas the core autophagic machineries required for Atg8 lipidation and vesiculation are essential for both routes, the upstream Atg1 …

D-Place: A Global Database Of Cultural, Linguistic And Environmental Diversity, Kathryn R. Kirby, Russell D. Gray, Simon J. Greenhill, Fiona M. Jordan, Stephanie Gomes-Ng, Hans-Jörg Bibiko, Damián E. Blasi, Carlos A. Botero, Claire Bowern, Carol R. Ember, Dan Leehr, Bobbi S. Low, Joe Mccarter, William Divale, Michael C. Gavin

Biology Faculty Research

From the foods we eat and the houses we construct, to our religious practices and political organization, to who we can marry and the types of games we teach our children, the diversity of cultural practices in the world is astounding. Yet, our ability to visualize and understand this diversity is limited by the ways it has been documented and shared: on a culture-by-culture basis, in locally-told stories or difficult-to-access repositories. In this paper we introduce D-PLACE, the Database of Places, Language, Culture, and Environment. This expandable and open-access database (accessible at https://d-place.org) brings together a dispersed corpus of …

Engineering Cre Recombinase For Genome Engineering, Chi Zhang

Arts & Sciences Graduate Student Theses and Dissertations

Cre recombinase recombines its DNA target, loxP sites, without help of accessory proteins or DNA repair systems. The simplicity of Cre-lox system has been widely utilized for genome editing, especially in mouse genetics. The goal of this dissertation is to constructCrerecombinase variants that will operate uponrecombination target sites (RTs) present within the genome, instead of perturbing the genome by inserting wildtype RTs for subsequent genome engineering. In general, the desired RTs native to the genome are asymmetric. However, the loxP sequence is pseudo-palindromic, requiring a homotetrameric formation of Cre recombinase. As a first step, I broke the symmetry of Cre …

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 …