Life Sciences Commons^™

Rna Sequencing Analysis Of The Msl2msl3, Crl, And Ggps1 Mutants Indicates That Diverse Sources Of Plastid Dysfunction Do Not Alter Leaf Morphology Through A Common Signaling Pathway, Darron R. Luesse, Margaret E. Wilson, Elizabeth S. Haswell

Biology Faculty Publications & Presentations

Determining whether individual genes function in the same or in different pathways is an important aspect of genetic analysis. As an alternative to the construction of higher-order mutants, we used contemporary expression profiling methods to perform pathway analysis on several Arabidopsis thaliana mutants, including the mscS-like (msl)2msl3 double mutant. MSL2 and MSL3 are implicated in plastid ion homeostasis, and msl2msl3 double mutants exhibit leaves with a lobed periphery, a rumpled surface, and disturbed mesophyll cell organization. Similar developmental phenotypes are also observed in other mutants with defects in a range of other chloroplast or mitochondrial functions, including …

Ubiquitin Goes Green, Zhihua Hua, Richard D. Vierstra

Biology Faculty Publications & Presentations

Chloroplasts depend on the nucleus for much of their proteome. Consequently, strong transcriptional coordination exists between the genomes, which is attuned to the developmental and physiological needs of the organelle. Recent studies highlight that the post-translational modifier ubiquitin adds another layer to plastid homeostasis and even helps eliminate damaged chloroplasts.

Stochastic Models For Plant Microtubule Self-Organization And Structure, Ezgi Can Eren, Ram Dixit, Natarajan Gautam

Biology Faculty Publications & Presentations

One of the key enablers of shape and growth in plant cells is the cortical microtubule (CMT) system, which is a polymer array that forms an appropriately-structured scaffolding in each cell. Plant biologists have shown that stochastic dynamics and simple rules of interactions between CMTs can lead to a coaligned CMT array structure. However, the mechanisms and conditions that cause CMT arrays to become organized are not well understood. It is prohibitively time-consuming to use actual plants to study the effect of various genetic mutations and environmental conditions on CMT self-organization. In fact, even computer simulations with multiple replications are …

Mechanosensitive Channel Msl8 Regulates Osmotic Forces During Pollen Hydration And Germination, Eric S. Hamilton, Gregory S. Jensen, Grigory Maksaev, Andrew Katims, Ashley M. Sherp, Elizabeth S. Haswell

Biology Faculty Publications & Presentations

Pollen grains undergo dramatic changes in cellular water potential as they deliver the male germ line to female gametes, and it has been proposed that mechanosensitive ion channels may sense the resulting mechanical stress. Here, we identify and characterize MscS-like 8 (MSL8), a pollen-specific, membrane tension–gated ion channel required for pollen to survive the hypoosmotic shock of rehydration and for full male fertility. MSL8 negatively regulates pollen germination but is required for cellular integrity during germination and tube growth. MSL8 thus senses and responds to changes in membrane tension associated with pollen hydration and germination. These data further suggest that …

Migration In The Social Stage Of Dictyostelium Discoideum Amoebae Impacts Competition, Chandra N. Jack, Neil J. Buttery, Boahemaa Adu-Oppong, Michael Powers, Christopher R.L. Thompson, David Queller, Joan E. Strassmann

Biology Faculty Publications & Presentations

Interaction conditions can change the balance of cooperation and conflict in multicellular groups. After aggregating together, cells of the social amoeba Dictyostelium discoideum may migrate as a group (known as a slug) to a new location. We consider this migration stage as an arena for social competition and conflict because the cells in the slug may not be from a genetically homogeneous population. In this study, we examined the interplay of two seemingly diametric actions, the solitary action of kin recognition and the collective action of slug migration in D. discoideum, to more fully understand the effects of social competition …

Wildfire Disturbance And Productivity As Drivers Of Plant Species Diversity Across Spatial Scales, Laura A. Burkle, Jonathan A. Myers, R Travis Belote

Biology Faculty Publications & Presentations

Wildfires influence many temperate terrestrial ecosystems worldwide. Historical environmental heterogeneity created by wildfires has been altered by human activities and will be impacted by future climate change. Our ability to predict the impact of wildfire-created heterogeneity on biodiversity is limited because few studies have investigated variation in community composition (beta-diversity) in response to fire. Wildfires may influence beta-diversity through several ecological mechanisms. First, high-severity fires may decrease beta-diversity by homogenizing species composition when they create landscapes dominated by disturbance-tolerant or rapidly colonizing species. In contrast, mixed-severity fires may increase beta-diversity by creating mosaic landscapes containing habitats that support species with …

Disturbance Alters Beta-Diversity But Not The Relative Importance Of Community Assembly Mechanisms, Jonathan A. Myers, Jonathan M. Chase, Raelene M. Crandall, Iván Jiménez

Biology Faculty Publications & Presentations

1. Ecological disturbances are often hypothesized to alter community assembly processes that influence variation in community composition (β-diversity). Disturbance can cause convergence in community composition (low β-diversity) by increasing niche selection of disturbance-tolerant species. Alternatively, disturbance can cause divergence in community composition (high β-diversity) by increasing habitat filtering across environmental gradients. However, because disturbance may also influence β-diversity through random sampling effects owing to changes in the number of individuals in local communities (community size) or abundances in the regional species pool, observed patterns of β-diversity alone cannot be used to unambiguously discern the relative importance of community assembly mechanisms.
2. We …

O6-Methylguanosine Leads To Position-Dependent Effects On Ribosome Speed And Fidelity, Benjamin H. Hudson, Hani S. Zaher

Biology Faculty Publications & Presentations

Nucleic acids are under constant assault from endogenous and environmental agents that alter their physical and chemical properties. O6-methylation of guanosine (m(6)G) is particularly notable for its high mutagenicity, pairing with T, during DNA replication. Yet, while m(6)G accumulates in both DNA and RNA, little is known about its effects on RNA. Here, we investigate the effects of m(6)G on the decoding process, using a reconstituted bacterial translation system. m(6)G at the first and third position of the codon decreases the accuracy of tRNA selection. The ribosome readily incorporates near-cognate aminoacyl-tRNAs (aa-tRNAs) by forming m(6)G-uridine codon-anticodon pairs. Surprisingly, the introduction …

Escherichia Coli Iron Acquisition Paradigms And Host Responses In The Human Urinary Milieu, Robin Reid Shields-Cutler

Arts & Sciences Electronic Theses and Dissertations

Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are increasingly complicated by high antibiotic resistance and recurrence rates. Explanations for the marked individual differences in UTI susceptibility remain incomplete. In this thesis we show that urinary colonization by uropathogenic E. coli (UPEC) is influenced by urine composition and the activity of an important innate immune protein, siderocalin (SCN; also called lipocalin 2 or neutrophil gelatinase-associated lipocalin/NGAL). During UTI, host factors limit the availability of iron, an essential nutrient for the invading pathogen. In response, UPEC modify the urinary environment with metal binding siderophores, some …

Peripheral And Central Mechanisms Of Temporal Pattern Recognition, Christa Ann Baker

Arts & Sciences Electronic Theses and Dissertations

Encoding information into the timing patterns of action potentials, or spikes, is a strategy used broadly in neural circuits. This type of coding scheme requires downstream neurons to be sensitive to the temporal patterns of presynaptic inputs. Indeed, neurons with temporal filtering properties have been found in a wide range of sensory pathways. However, how such response properties arise was previously not well understood. The goal of my dissertation research has been to elucidate how temporal filtering by single neurons contributes to the behavioral ability to recognize timing patterns in communication signals.

I have addressed this question using mormyrid weakly …

A Gnotobiotic Mouse Model For Studying The Effect Of Human Gut Community Ecology On A Pathobiont, Bacteroides Fragilis, Vitas Wagner

Arts & Sciences Electronic Theses and Dissertations

ABSTRACT OF THE DISSERTATION

A Gnotobiotic Mouse Model for Studying the Effect of Human Gut Community Ecology on a Pathobiont, Bacteroides fragilis

by

Vitas Wagner

Doctor of Philosophy in Biology and Biomedical Sciences

Evolution, Ecology, and Population Biology

Washington University in St. Louis, 2015

Professor Jeffrey I. Gordon, Chair

Childhood undernutrition represents a pressing global health challenge. Epidemiologic studies have shown that undernutrition is not due to food insecurity alone, but rather represents a complex set of interactions between intra- and intergenerational factors. The gut microbiota has been implicated as one such factor. This thesis tested the hypothesis that enteropathogen …

Programming The Myocardium: The Notch-Wnt Axis, Benjamin S. Gillers

Arts & Sciences Electronic Theses and Dissertations

Heart related deaths are the number one cause of death in the United States. While heart failure and other mechanical issues are common, arrhythmias account for the majority of these deaths. By understanding the genetic architecture that patterns the normal cardiac conduction system, we can further deepen our understanding of how arrhythmias arise and develop targeted therapies to treat this deadly class of disease. I have found that canonical Wnt signaling is necessary for development of the atrioventricular junction. Furthermore, absence of myocardial Wnt signaling leads to tricuspid atresia. Overexpression of Wnt signaling leads to development of ectopic atrioventricular junction …

Flap Endonuclease 1 Promotes Telomere Replication And Stability By Distinct Mechanisms On The Leading And Lagging Strands, Daniel Cole Teasley

Arts & Sciences Electronic Theses and Dissertations

High fidelity DNA replication is essential for genomic stability and cell survival; this fact is underscored by the redundancy present in DNA replication and repair pathways. The complexity of these pathways is most evident at challenging DNA templates, such as those with repetitive sequence and transcribed loci. Among these challenging templates are telomeres, which are terminal, highly repetitive sequences that maintain genomic stability by preventing aberrant end-to-end chromosome fusions. In the absence of accurate, complete telomere replication, genomic instability results, ultimately leading to cell death or transformation. Here, we describe two unique roles in telomere stability for the DNA replication …

Neural Basis Of Functional Connectivity Mri, Jingfeng Li

Arts & Sciences Electronic Theses and Dissertations

The brain is hierarchically organized across a range of scales. While studies based on electrophysiology and anatomy have been fruitful on the micron to millimeter scale, findings based on functional connectivity MRI (fcMRI) suggest that a higher level of brain organization has been largely overlooked. These findings show that the brain is organized into networks, and each network extends across multiple brain areas. This large-scale, across-area brain organization is functionally relevant and stable across subjects, primate species, and levels of consciousness.

This dissertation addresses the neural origin of MRI functional connectivity. fcMRI relies on temporal correlation in at-rest blood oxygen …

Host Immune Signals Regulate Blood-Brain Barrier Function During Central Nervous System Infection And Autoimmunity, Brian Daniels

Arts & Sciences Electronic Theses and Dissertations

A major hallmark of neuroinflammatory diseases is the breakdown of the blood-brain barrier (BBB). This barrier between the hematogenous circulation and the parenchyma of the central nervous system (CNS) is a multicellular interface made up of endothelial cells joined by tight and adherens junctions (TJs and AJs), along with pericytes and the endfeet projections of astroglia. Together, these cells tightly restrict the movement of solutes and cells from the circulation into the CNS in a manner crucial for proper CNS homeostasis. Regulation of BBB function occurs dynamically during neuroinflammatory diseases such as infection and CNS autoimmunity, resulting in both protective …

Spatial And Epigenetic Regulation Of T-Cell Receptor Beta Gene Assembly, Kinjal Majumder

Arts & Sciences Electronic Theses and Dissertations

The adaptive immune system endows mammals with a sophisticated mechanism to recognize foreign proteins via surface antigen receptors that are expressed on the surface of all lymphocytes. This defense network is generated by V(D)J recombination, a set of sequentially controlled DNA cleavage and repair events that assembles functional antigen receptor genes from distally located Variable (V), Diversity (D) and Joining (J) gene segments. However, the recombination process must be stringently regulated to prevent formation of chromosomal translocations, which can lead to tumors. The process of V(D)J recombination is controlled at the levels of tissue, stage and allele specificity by a …

Β-Lactamase Gene Exchange Within The Enterobacteriaceae, Mitchell William Pesesky

Arts & Sciences Electronic Theses and Dissertations

Antibiotic resistance represents a grave threat to modern medicine’s control over infectious disease. Pathogens of the Enterobacteriaceae have proven particularly problematic as they can cause a wide variety of infections, and they can be, in some cases, resistant to all antibiotics recommended for use against them. A major part of the threat posed by the Enterobacteriaceae is their ability to exchange resistance genes by horizontal gene transfer (HGT). HGT has allowed some Enterobacteriaceae to quickly accumulate resistance against diverse antibiotics, and then to spread their resistance gene collection to other pathogenic strains. I explore three aspects of how HGT has …

Evolutionary Developmental Leaf Morphology Of The Plant Family Araceae, Claudia Liliana Henriquez

Arts & Sciences Electronic Theses and Dissertations

Studying the evolutionary developmental morphology of leaves using next-generation phylogenetics, a candidate gene approach and comparative developmental studies in the plant family Araceae is the overarching theme of the dissertation.

The plant family Araceae is an ancient lineage from the Early Cretaceous and belongs to the monocotyledons. Members of Araceae display striking variation in leaf development; such variation contradicts traditional models of monocot leaf development. Additionally, dissected leaves, which are rare in monocots, seem to have evolved independently multiple times in Araceae by various developmental mechanisms.

Despite extensive efforts to elucidate the evolutionary history of Araceae, phylogenetic ambiguity in the …

Functional Identification And Characterization Of Cis-Regulatory Elements, Christopher Michael Fiore

Arts & Sciences Electronic Theses and Dissertations

Transcription is regulated through interactions between regulatory proteins, such as transcription factors (TFs), and DNA sequence. It is known that TFs act combinatorially in some cases to regulate transcription, but in which situations and to what degree is unclear.

I first studied the contribution of TF binding sites to expression in mouse embryonic stem (ES) cells by using synthetic cis-regulatory elements (CREs). The synthetic CREs were comprised of combinations of binding sites for the pluripotency TFs Oct4, Sox2, Klf4, and Esrrb. A statistical thermodynamic model explained 72% of the variation in expression driven by these CREs. The high predictive power …

A Novel Cholesterol-Independent Mode Of Binding Promotes Cytolysin-Mediated Translocation And Pore Formation By Streptolysin O, Cara Mozola Forsberg

Arts & Sciences Electronic Theses and Dissertations

Effector translocation is a common strategy used by bacteria to promote pathogenesis via disruption of the immune response, prevention of phagocytosis, or induction of toxicity in the infected cell. The Gram-positive bacterium Streptococcus pyogenes utilizes a unique effector translocation system termed cytolysin-mediated translocation (CMT) to introduce the NAD+ glycohydrolase SPN into host cells during infection, resulting in cytotoxicity. Host cell membrane recognition by the cholesterol-dependent cytolysin (CDC) Streptolysin O (SLO) is a requisite step in this process, but the canonical cholesterol-dependent pore-forming activity of SLO is unnecessary, indicating that SLO is a bifunctional toxin. SLO exhibits extensive homology to other …

The Role Of Tmem178 In Regulation Of Osteo-Immune Activation And Inflammatory Bone Loss, Corinne Elaine Decker

Arts & Sciences Electronic Theses and Dissertations

Pathological bone loss in human disease such as arthritis is largely due to excessive osteoclast recruitment as a consequence of localized inflammation. Innate immune cells, namely neutrophils and macrophages, infiltrate the joint space and release pro-inflammatory cytokines as well as proteases to drive local tissue damage and inflammation. Importantly, IL-1 and TNF-a in particular act on the synovial fibroblasts as well as directly on osteoclast precursors to potently augment osteoclast differentiation and thus bone resorption. Current therapeutics to treat pathological bone loss are widely unsuccessful at targeting both the resorptive and inflammatory components of disease. We have previously demonstrated that …

Neural Mechanisms Of Working Memory Cortical Networks, Charalampos Papadimitriou

Arts & Sciences Electronic Theses and Dissertations

This dissertation is aimed at understanding the cortical networks that maintain working memory information. By leveraging patterns of information degradation in spatial working memory encoding we reveal new neural mechanisms that support working memory function and challenge existing models of working memory circuits.

First we examine how interference from previous memoranda influences memory of a currently remembered location. We find that memory for a currently remembered location is biased toward the previously memorized location. This interference is graded, not all-or-none. Interference is strongest when the previous and current targets are close and activate overlapping populations of neurons. Contrary to the …

Characterizing And Modeling Antibiotic Resistance Dynamics In Diverse Microbial Communities, Molly Krisann Gibson

Arts & Sciences Electronic Theses and Dissertations

Complex microbial communities colonize every habitat investigated to date, including soil, animals, water, and humans, as well as the structures we live in. It has been hypothesized that there is network of exchange allowing both bacterial organisms and functions to seamlessly move between and within these environments. These microbial communities often serve essential and beneficial functions for the host organism or environment. This is particularly evident in the human gut, where microbial communities consistently provide a set of services to its human host, including protecting against enteric pathogens, liberating nutrients from food, and signaling immune system regulation. However, these communities …

Essential Roles Of Stat3 In Zebrafish Development, Yinzi Liu

Arts & Sciences Electronic Theses and Dissertations

Vertebrate gastrulation is a fundamental morphogenetic process during which germ layers are formed, patterned and shaped into a body plan with organ rudiments. Among the conserved gastrulation movements, convergence and extension (C&E) occur concurrently to narrow the germ layers mediolaterally and elongate them along the anteroposterior embryonic axis. C&E are largely driven by cell migration and cell intercalation, while cell proliferation has been considered dispensable and even incompatible with gastrulation movements and morphogenesis. Signal transducer and activator of transcription 3 (Stat3) has been implicated by antisense morpholino loss-of-function study in regulation of zebrafish C&E movements in part by promoting non …

Dissection Of Affective Catecholamine Circuits Using Traditional And Wireless Optogenetics, Jordan Gary Mccall

Arts & Sciences Electronic Theses and Dissertations

Parsing the complexity of the mammalian brain has challenged neuroscientists for thousands of years. In the early 21st century, advances in materials science and neuroscience have enabled unprecedented control of neural circuitry. In particular, cell-type selective manipulations, such as those with optogenetics and chemogenetics, routinely provide answers to previously intractable neurobiological questions in the intact, behaving animal.

In this two-part dissertation, I first introduce new minimally invasive, wireless technology to perturb neural activity in the ventral tegmental area dopaminergic system of freely moving animals. I report a series of novel devices for studying and perturbing intact neural systems through optogenetics, …

A Search For Parent-Of-Origin Effects On Honey Bee Gene Expression, Sarah D. Kocher, Jennifer M. Tsuruda, Joshua D. Gibson, Christine M. Emore, Miguel E. Arechavaleta-Velasco, David C. Queller, Joan E. Strassmann, Christina M. Grozinger, Michael R. Gribskov, Phillip San Miguel, Rick Westerman, Greg J. Hunt

Biology Faculty Publications & Presentations

Parent-specific gene expression (PSGE) is little known outside of mammals and plants. PSGE occurs when the expression level of a gene depends on whether an allele was inherited from the mother or the father. Kin selection theory predicts that there should be extensive PSGE in social insects because social insect parents can gain inclusive fitness benefits by silencing parental alleles in female offspring. We searched for evidence of PSGE in honey bees using transcriptomes from reciprocal crosses between European and Africanized strains. We found 46 transcripts with significant parent-of-origin effects on gene expression, many of which overexpressed the maternal allele. …

Fuels And Fires Influence Vegetation Via Above- And Belowground Pathways In A High-Diversity Plant Community, Paul R. Gagnon, Heather A. Passmore, Matthew Slocum, Jonathan A. Myers, Kyle E. Harms, William J. Platt, C.E. Timothy Paine

Biology Faculty Publications & Presentations

1. Fire strongly influences plant populations and communities around the world, making it an important agent of plant evolution. Fire influences vegetation through multiple pathways, both above- and belowground. Few studies have yet attempted to tie these pathways together in a mechanistic way through soil heating even though the importance of soil heating for plants in fire-prone ecosystems is increasingly recognized.
2. Here we combine an experimental approach with structural equation modelling (SEM) to simultaneously examine multiple pathways through which fire might influence herbaceous vegetation. In a high-diversity longleaf pine groundcover community in Louisiana, USA, we manipulated fine-fuel biomass and monitored the …

Genomic Signatures Of Cooperation And Conflict In The Social Amoeba, Elizabeth A. Ostrowski, Yufeng Shen, Xiangjun Tian, Richard Sucgang, Huaiyang Jiang, Jiaxin Qu, Mariko Katoh-Kurasawa, Debra A. Brock, Christopher Dinh, Fremiet Lara-Garduno, Sandra L. Lee, Christie L. Kovar, Huyen H. Dinh, Viktoriya Korchina, Laronda Jackson, Shobha Patil, Yi Han, Lesley Chaboub, Gad Shaulsky, Donna M. Muzny, Kim C. Worley, Richard A. Gibbs, Stephen Richards, Adam Kuspa, Joan E. Strassmann, David C. Queller

Biology Faculty Publications & Presentations

• Molecular evolution analyses reveal the history of social conflict
• Genes that mediate social conflict show signatures of frequency-dependent selection
• Balanced polymorphisms suggest that cheating may be stable and endemic

Cooperative systems are susceptible to invasion by selfish individuals that profit from receiving the social benefits but fail to contribute. These so-called "cheaters" can have a fitness advantage in the laboratory, but it is unclear whether cheating provides an important selective advantage in nature. We used a population genomic approach to examine the history of genes involved in cheating behaviors in the social amoeba Dictyostelium discoideum, testing whether these genes experience …

Erika Dyck. Facing Eugenics: Reproduction, Sterilization, And The Politics Of Choice, Garland E. Allen

Biology Faculty Publications & Presentations

[Book review of Erika Dyck. Facing Eugenics: Reproduction, Sterilization, and the Politics of Choice. Toronto: University of Toronto Press, 2013.]

Expressing And Characterizing Mechanosensitive Channels In Xenopus Oocytes, Grigory Maksaev, Elizabeth S. Haswell

Biology Faculty Publications & Presentations

The oocytes of the African clawed frog (Xenopus laevis) comprise one of the most widely used membrane protein expression systems. While frequently used for studies of transporters and ion channels, the application of this system to the study of mechanosensitive ion channels has been overlooked, perhaps due to a relative abundance of native expression systems. Recent advances, however, have illustrated the advantages of the oocyte system for studying plant and bacterial mechanosensitive channels. Here we describe in detail the methods used for heterologous expression and characterization of bacterial and plant mechanosensitive channels in Xenopus oocytes.