Biology Commons^™

The Mechanism And Regulation Of Mammalian Photoreceptor Dark Adaptation, Yunlu Xue

Arts & Sciences Graduate Student Theses and Dissertations

The visual perception of vertebrates begins in rod and cone photoreceptors. Both photoreceptors require visual pigments to detect light. At the first step of light detection, a chromophore molecule (i.e. 11-cis retinal), which is conjugated to the visual pigment in photoreceptor outer segment, absorbs a photon. Photoisomerization of the chromophore activates the visual pigment, triggers the phototransduction cascade, and produces electrical signals. After photoisomerization, the chromophore is ultimately converted to all-trans retinol, which must be recycled to regenerate the visual pigment. This visual pigment regeneration process is called the visual cycle. It is the rate-limiting step of the photoreceptor dark …

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

Biology Faculty Research

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 Research

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 Research

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 Research

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 Research

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 Research

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 …

Neural Mechanisms Of Working Memory Cortical Networks, Charalampos Papadimitriou

Arts & Sciences Graduate Student 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 attractive …

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

Arts & Sciences Graduate Student 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 …

Adaptive Mechanisms Of Niche Remodeling In Streptococcus Pyogenes, Elyse Paluscio

Arts & Sciences Graduate Student Theses and Dissertations

The Gram-positive bacterium Streptococcus pyogenes is a remarkably successful pathogen, capable of infecting numerous tissue sites within its human host. The ability of S. pyogenes to invade these different niches is, in part, due to the species’ ability to monitor various physical and chemical signals in its environment and alter its transcriptional profile in response to these differential conditions. As a member of the lactic acid bacteria, S. pyogenes has a simple fermentative metabolism and relies exclusively on a combination of homo-lactic and mixed acid fermentation as a means of generating energy in the cell. As a consequence of its …

Dna Damage Responses Regulate Macrophage Function During Innate Immune Responses, Abigail Rodriguez Morales

Arts & Sciences Graduate Student Theses and Dissertations

Activated macrophages produce genotoxins such as reactive oxygen and nitrogen intermediates that are critical for the eradication of pathogens. Here we show that one of these agents, nitric oxide (NO), damages macrophage genomic DNA, resulting in the activation of DNA damage responses (DDR). The DDR is primarily initiated through DNA double-strand break (DSB) intermediates and depends on the PI3-like kinases ATM and DNA-PKcs. In response to Listeria monocytogenes infection, ATM and DNA-PKcs regulate a tissue-specific genetic program that includes the expression of inflammatory cytokines, chemokines and cell surface receptors, several of which are critical for cell migration during immune responses …

The Role Of Reversible Palmitoylation In Regulating Diverse Biological Processes, Mohammad H. Maktabi

Arts & Sciences Graduate Student Theses and Dissertations

It is well established that covalent lipid-modification of proteins can play an important role in the spatial and temporal organization of many intracellular signaling proteins. In particular, protein palmitoylation, the thioester linkage of a palmitate moiety to a cysteine residue, plays a critical role in promoting membrane binding. It also serves as a versatile sorting signal for membrane trafficking and precise microdomain partitioning. Classical studies using metabolic labeling have revealed that palmitoylation is dynamic, in which many substrates undergo palmitate cycling, and that turnover is regulated by extracellular signals. As such, the kinetics of palmitoylation cycling is dependent on the …

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

Arts & Sciences Graduate Student 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 …

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

Arts & Sciences Graduate Student 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 …

Essential Roles Of Stat3 In Zebrafish Development, Yinzi Liu

Arts & Sciences Graduate Student 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 …

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

Arts & Sciences Graduate Student 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 …

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

Arts & Sciences Graduate Student 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, microfluidic …

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

Arts & Sciences Graduate Student 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 …

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

Arts & Sciences Graduate Student Theses and Dissertations

ABSTRACT OF THE DISSERTATIONA Gnotobiotic Mouse Model for Studying the Effect of Human Gut Community Ecology on a Pathobiont, Bacteroides fragilisbyVitas WagnerDoctor of Philosophy in Biology and Biomedical SciencesEvolution, Ecology, and Population BiologyWashington University in St. Louis, 2015Professor Jeffrey I. Gordon, ChairChildhood 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 burden affects the structure and expressed functions of …

Genetic Factors That Contribute To The Pathogenesis Of Amyotrophic Lateral Sclerosis, Janet Elizabeth Cady

Arts & Sciences Graduate Student Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is fatal neurodegenerative disease for which there is no cure. The only treatment available extends survival by only a matter of months. There are over 20 genes that are known to cause ALS. Over half of the ALS cases with a family history of disease (FALS) can be explained by mutations in known ALS genes with hexanucleotide repeat expansions in C9ORF72 accounting for 40% of families. However roughly 90% of cases have no family history of disease (sporadic ALS or SALS) and a much smaller proportion (10%) of these cases can be explained by mutations in …

Defining The Roles Of Outer Membrane Proteins And Host Cathelicidins In Uropathogenic Escherichia Coli Infection, Elizabeth Sarah Danka

Arts & Sciences Graduate Student Theses and Dissertations

The Gram-negative bacterium uropathogenic Escherichia coli (UPEC) is the causative agent of up to 85% of community-acquired urinary tract infections (UTIs). This thesis work aimed to better define interactions between UPEC and host antimicrobial peptides (AMPs). The bacterial outer membrane is constantly interacting with the external environment, and contains many integral proteins with defined roles in pathogenesis. The E. coli outer membrane protein OmpA is a highly conserved, integral beta-barrel membrane protein with four extracellular loops. We found that the loops of OmpA individually influence binding and invasion of UPEC during infection. Loop 2 appears to be essential for binding …

Variation And Plasticity Of Dna Methylation In Genome Regulation, Junchen Gu

Arts & Sciences Graduate Student Theses and Dissertations

DNA methylation is an important and well-studied epigenetic mark. It plays a pivotal role in imprinting, X-chromosome inactivation and genome stability and regulation in many normal development processes. DNA methylation, along with histone modifications, orchestrates the cell type- and developmental stage-specific chromatin landscapes and influences gene expression in vertebrates. In this thesis, I utilized the latest next-generation sequencing based methods to map DNA methylation levels at a genome-wide scale to investigate two areas of interest: the variation of DNA methylation across a large number of sample types and its functional potentials; the plasticity of DNA methylation in response to environmental …

Mechanisms Underlying Memory Deficits Following West Nile Virus Neuroinvasive Disease, Michael John Vasek

Arts & Sciences Graduate Student Theses and Dissertations

Neurocognitive sequelae are observed in >50% of patients who survive neuroinvasive infections with encephalitic arboviruses, such as the mosquito-borne West Nile virus (WNV). Early diagnosis and high survival rates from WNV neuroinvasive disease (WNND) (>90%) have thus led cumulatively to approximately ten thousand patients living with neurocognitive impairments, with 1-3000 cases accruing yearly, yet underlying mechanisms responsible for these deficits have not been investigated.Within the last 15 years, studies have begun uncover many pathways which are utilized both by the developing CNS as well as the immune system, including the use of cytokines in the regulation of progenitor cell …

Functional Characterization Of Putative Rab Geranylgeranyltransferase Subunits In Arabidopsis Thaliana, Wan Shi

Arts & Sciences Graduate Student Theses and Dissertations

Protein prenylation is one of the posttranslational lipid modifications that facilitate protein-membrane association and protein-protein interactions. Three types of heterodimeric protein prenyltransferases, protein farnesyltransferase (PFT), protein geranylgeranyltransferase-I (PGGT-I), and protein geranylgeranyltransferase-II or Rab geranylgeranyltransferase (Rab-GGT), are present in all eukaryotes. In Arabidopsis there are two putative genes encoding Rab-GGT α subunits, termed RGTA1 and RGTA2, and two putative genes encoding β subunits, RGTB1 and RGTB2, but little is known about Arabidopsis Rab-GGT activity. In this dissertation, I demonstrate that four different heterodimers can be formed between RGTA1, RGTA2, RGTB1, and RGTB2, but only RGTA1-RGTB1 and RGTA1-RGTB2 exhibit bona fide Rab-GGT …

Atypical Cadherin Dachsous Regulates The Cytoskeleton And Gastrulation Movements During Zebrafish Development, Nanbing Li

Arts & Sciences Graduate Student Theses and Dissertations

Dachsous (Dchs), an evolutionarily conserved atypical cadherin, regulates planar cell polarity, tissue size, and cell adhesion in Drosophila. However, its functions in vertebrates are just beginning to be elucidated. Inactivating one of two murine homologs, Dchs1, leads to multi-organ defects and postnatal lethality. Recent studies in humans suggest that mutations in DCHS1 cause pleiotropic Van Maldergem syndrome. My thesis work focuses on the functional characterization of zebrafish dchs1b and dchs2 genes. Mutations in dchs1b and dchs2 genes affect several aspects of embryogenesis, including gastrulation. Unexpectedly, dchs1b is also essential for the earliest vertebrate developmental stage, egg activation. We show that …

Neural Basis Of Functional Connectivity Mri, Jingfeng Li

Arts & Sciences Graduate Student 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 level …

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

Arts & Sciences Graduate Student 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 …

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

Arts & Sciences Graduate Student 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 …

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

Arts & Sciences Graduate Student 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 backbone of …

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

Arts & Sciences Graduate Student 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 of …