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Full-Text Articles in Biology

Correlated Variability And Adaptation In Orbitofrontal Cortex During Economic Choice, Katherine E. Conen May 2018

Correlated Variability And Adaptation In Orbitofrontal Cortex During Economic Choice, Katherine E. Conen

Arts & Sciences Graduate Student Theses and Dissertations

Economic decision-making requires the computation and comparison of subjective values. Several lines of evidence suggest that these processes are mediated by circuits in orbitofrontal cortex (OFC). Neurons in OFC encode the subjective values of choice options and outcomes, and damage to this area leads to selective deficits in value-guided behavior. To understand the nature of choice more thoroughly, it is useful to consider the features of OFC circuits that can limit or enhance information processing. In this document, I present work examining two factors that influence encoding in OFC: noise correlation and value adaptation. In the first study, I show …


Integration Of Local And Regional Regulatory Information In The Human Genome, Hemangi Govind Chaudhari May 2018

Integration Of Local And Regional Regulatory Information In The Human Genome, Hemangi Govind Chaudhari

Arts & Sciences Graduate Student Theses and Dissertations

Gene regulation involves the integration of different sources of information at multiple levels. The action of transcription factors is integrated at cis-regulatory sequences (CRSs). Information from many CRSs is combined to drive spatiotemporally regulated gene expression. Prediction of CRS activity from DNA sequence is challenging because most occurrences of transcription factor binding sites (TFBS) are not functional. I assayed the activity of thousands of genomic sequences with Activator Protein 1 (AP-1) binding sites in K562 cells to identify features in flanking sequences that distinguish functional from non-functional TFBS. I find that sequence features directly adjacent to the AP-1 core motif, …


Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar May 2018

Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar

Arts & Sciences Graduate Student Theses and Dissertations

Paired tumor-normal sequencing of thousands of patient’s exomes has revealed millions of somatic mutations, but functional characterization and clinical decision making are stymied because biologically neutral ‘passenger’ mutations greatly outnumber pathogenic ‘driver’ mutations. Since most mutations will return negative results if tested, conventional resource-intensive experiments are reserved for mutations which are observed in multiple patients or rarer mutations found in well-established cancer genes. Most mutations are therefore never tested, diminishing the potential to discover new mechanisms of cancer development and treatment opportunities. Computational methods that reliably prioritize mutations for testing would greatly increase the translation of sequencing results to clinical …


Multi-Omics Portraits Of Cancer, Kuan-Lin Huang May 2018

Multi-Omics Portraits Of Cancer, Kuan-Lin Huang

Arts & Sciences Graduate Student Theses and Dissertations

Precision oncology demands accurate portrayal of a disease at all molecular levels. However, current large-scale studies of omics are often isolated by data types. I have been developing computational tools to conduct integrative analyses of omics data, identifying unique molecular etiology in each tumor. Particularly, this dissertation presents the following contributions to the computational omics of cancer: (1) uncovering the predisposition landscape in 33 cancers and how germline genome collaborates with somatic alterations in oncogenesis; (2) pioneering methods to combine genomic and proteomic data to identify treatment opportunities; and (3) revealing selective phosphorylation of kinase-substrate pairs. These findings advance our …


The Role Of Actr10 In Nervous System Development And Disease, Amy Herbert May 2018

The Role Of Actr10 In Nervous System Development And Disease, Amy Herbert

Arts & Sciences Graduate Student Theses and Dissertations

The vertebrate nervous system requires myelinating glia for the fast propagation of action potentials, as well as for vital trophic support to axons. Myelinating glia produce myelin, which is a lipid-rich, multi-lamellar sheath that surrounds axons and allows for rapid electrical signaling. In the central nervous system (CNS), myelin is produced by oligodendrocytes, while in the peripheral nervous system (PNS), Schwann cells perform this function. Although glia have historically been understudied compared to neurons, recent research has uncovered critical roles for glia in nervous system development and disease. Disruption to myelin or to the glial cells that generate myelin can …


The Ugly Sequestosome1:The Role Of P62/Sqstm1 In Autophagy And Multisystem Proteinopathy, Eugene Lee May 2018

The Ugly Sequestosome1:The Role Of P62/Sqstm1 In Autophagy And Multisystem Proteinopathy, Eugene Lee

Arts & Sciences Graduate Student Theses and Dissertations

Multisystem proteinopathy (MSP) defines a spectrum of degenerative diseases unified by TDP-43 pathology that affect muscle, brain and bone. Mutations in several proteins (VCP, p62/SQSTM1, HNRNPA2B1, HNRNPA1) can all cause MSP via impairments in autophagic protein degradation (VCP and SQSTM1) or RNA granule dynamics (HNRNPA2B1 and HNRNPA1). Phenotypically, MSP mutations lead to variable penetrance of several phenotypes: Paget’s disease of the bone (PDB), rimmed vacuolar inclusion body myopathy (RV-IBM), amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). However, how a same mutation of a protein can develop different diseases remains unclear. Understanding of p62/SQSTM1 (SQSTM1) function is critical to answer …


Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer May 2018

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Graduate Student Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …


Defining Neuronal Identity Using Microrna-Mediated Reprogramming, Matthew James Mccoy May 2018

Defining Neuronal Identity Using Microrna-Mediated Reprogramming, Matthew James Mccoy

Arts & Sciences Graduate Student Theses and Dissertations

Cell fate reprogramming is transforming our understanding of the establishment and maintenance of cellular identity. In addition, reprogramming holds great promise to model diseases affecting cell types that are prohibitively difficult to study, such as human neurons. Overexpression of the brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124) results in reprogramming human somatic cells into neurons and has recently been used to generate specific neuronal subtypes affected in neurodegenerative disorders. However, the mechanisms governing the ability of miR-9/9*-124 to generate alternative subtypes of neurons remained unknown. In this thesis, I report that overexpressing miR-9/9*-124 triggers reconfiguration of chromatin accessibility, DNA methylation, …


Innate Lymphoid Cells: Transcriptional Profiles And Cytokine Developmental Requirements, Michelle Lauren Robinette May 2018

Innate Lymphoid Cells: Transcriptional Profiles And Cytokine Developmental Requirements, Michelle Lauren Robinette

Arts & Sciences Graduate Student Theses and Dissertations

Innate lymphoid cells (ILCs) are a recently discovered lineage of professional cytokine-producing cells that strikingly mirror T cells in transcriptional circuitry and effector functions, but derive from distinct progenitors and do not express recombined antigen-specific receptors. These cells include natural killer (NK) cells, which parallel cytotoxic CD8+ T cells, and three additional classes of ILCs enriched at mucosal surfaces that generate signature cytokines reminiscent of polarized CD4+ helper T cells subsets, called ILC1, ILC2, and ILC3. As ILCs have been implicated in the pathogenesis of colitis, cancer, allergy, and autoimmunity in both human and mouse, understanding the functional capacity of …


Sex Differences In Uropathogenic Escherichia Coli Urinary Tract Infection, Patrick David Olson May 2018

Sex Differences In Uropathogenic Escherichia Coli Urinary Tract Infection, Patrick David Olson

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are among the most common bacterial infections which plague humans. Community-onset UTI is widely viewed as a disease only of women; indeed, its occurrence between 2 and 60 years of age is almost exclusive to females. However, the disease also affects substantial male patient populations, namely infants and the very elderly. While female cases of complicated and upper-tract UTI (pyelonephritis) outnumber male cases overall, men carry an increased risk of mortality from these infections. Sex differences in UTI epidemiology have heretofore been attributed almost entirely to anatomic and hygienic factors in females, including the permissiveness of …


Circadian Regulation Of Temozolomide Sensitivity In Glioblastoma, Emily A. Slat May 2018

Circadian Regulation Of Temozolomide Sensitivity In Glioblastoma, Emily A. Slat

Arts & Sciences Graduate Student Theses and Dissertations

The safety and efficacy of multiple cancer chemotherapeutics can vary as a function of when during the day they are delivered. This study aimed to improve the treatment of glioblastoma multiforme (GBM), the most common brain cancer, by testing the efficacy of the DNA alkylator Temozolomide (TMZ) on GBM in vitro and in vivo as a function of time of day. We found cell-intrinsic, daily rhythms in susceptibility of GBM tumor cells (mouse astrocytes deficient in NF1 and p53 signaling) to TMZ in vitro. The greatest TMZ-induced DNA damage response, activation of apoptosis and growth inhibition, occurred near the peak …


Deciphering Mechanisms Governing The Development Of The Rod Epigenome, Philip Andrew Ruzycki May 2018

Deciphering Mechanisms Governing The Development Of The Rod Epigenome, Philip Andrew Ruzycki

Arts & Sciences Graduate Student Theses and Dissertations

Precisely coordinated expression of distinct sets of genes is essential for cellular development and function, especially in complex multicellular organisms. This regulation is achieved by the action of transcription factors (TF), proteins that bind specific genomic locations and alter the activity state and packaging of the DNA to promote or repress gene expression. However, while tremendous effort has defined networks of transcription factors that work together to drive specific phenotypes, little is known about their differential activity at the hundreds or thousands of sites where they bind. There are also many questions regarding the basic principles of the packaging of …


Characterizing The Role Of The T Cell Receptor Repertoire In T Cell Development And Function, Benjamin David Solomon May 2018

Characterizing The Role Of The T Cell Receptor Repertoire In T Cell Development And Function, Benjamin David Solomon

Arts & Sciences Graduate Student Theses and Dissertations

Expansion and memory of immune cells in response to stimulation of diversified antigen receptors is the hallmark of adaptive immunity. Here, we use antigen receptor sequencing and in vivo analysis of monoclonal cell populations to elucidate the development and function of two T cell populations: Foxp3+RORγt+ CD4+ T cells and γδ T cells. Foxp3+RORγt+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relation to RORγt- Treg and RORγt+ TH17 cells remains unclear. Here, we show that despite sharing a subset of TCR specificities with TH17 cells, …


Regulation Of Epithelial Proliferation And Migration By Apical-Basal Polarity Proteins, Gregory Vincent Schimizzi May 2018

Regulation Of Epithelial Proliferation And Migration By Apical-Basal Polarity Proteins, Gregory Vincent Schimizzi

Arts & Sciences Graduate Student Theses and Dissertations

Epithelial cells line all the outside surfaces of the body where they perform essential roles in maintaining homeostasis. In addition, epithelial tissues are implicated in many disease processes and are the most common tissue type to give rise to human cancer. Therefore, a thorough understanding of epithelial development and homeostasis has broad implications for understanding human development, health, and disease. The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Proper apical-basal polarity (ABP) is required for epithelial tissues to carry out their functions, which include absorption, secretion, barrier formation, and collective migration. …


Molecular Mediators Of Acute And Chronic Itch In Mouse And Human Sensory Neurons, Manouela Valtcheva May 2018

Molecular Mediators Of Acute And Chronic Itch In Mouse And Human Sensory Neurons, Manouela Valtcheva

Arts & Sciences Graduate Student Theses and Dissertations

Itch is a distinct sensation that arises from the activation of small-diameter pruriceptive nerve fibers innervating the skin. Recent strides in the field have identified several histamine-dependent and -independent pruriceptive pathways and receptors that contribute to acute and chronic itch. The work presented in this thesis further investigates the molecular mechanisms involved in the signaling, development, and sensitization of itch in mouse and human. Most pruritogen receptors are Gq-Protein Coupled Receptors (GqPCR), which canonically activate protein kinase C (PKC); however, little is known about whether specific PKC isoforms regulate itch. The first study in this thesis demonstrates that the isoform …


Predator-By-Environment Interactions Mediate Bacterial Competition In The Dictyostelium Discoideum Microbiome, R Fredrik Inglis, Odion Asikhia, Erica Ryu, David C. Queller, Joan E. Strassmann Apr 2018

Predator-By-Environment Interactions Mediate Bacterial Competition In The Dictyostelium Discoideum Microbiome, R Fredrik Inglis, Odion Asikhia, Erica Ryu, David C. Queller, Joan E. Strassmann

Biology Faculty Research

Interactions between species and their environment play a key role in the evolution of diverse communities, and numerous studies have emphasized that interactions among microbes and among trophic levels play an important role in maintaining microbial diversity and ecosystem functioning. In this study, we investigate how two of these types of interactions, public goods cooperation through the production of iron scavenging siderophores and predation by the social amoeba Dictyostelium discoideum, mediate competition between two strains of Pseudomonas fluorescens that were co-isolated from D. discoideum. We find that although we are able to generally predict the competitive outcomes between …


An Insoluble Iron Complex Coated Cathode Enhances Direct Electron Uptake By Rhodopseudomonas Palustris Tie-1, Karthikeyan Rengasamy, Tahina Ranaivoarisoa, Rajesh Singh, Arpita Bose Apr 2018

An Insoluble Iron Complex Coated Cathode Enhances Direct Electron Uptake By Rhodopseudomonas Palustris Tie-1, Karthikeyan Rengasamy, Tahina Ranaivoarisoa, Rajesh Singh, Arpita Bose

Biology Faculty Research

Microbial electrosynthesis (MES) is a promising bioelectrochemical approach to produce biochemicals. A previous study showed that Rhodopseudomonas palustris TIE-1 can directly use poised electrodes as electron donors for photoautotrophic growth at cathodic potentials that avoid electrolytic H2 production (photoelectroautotrophy). To make TIE-1 an effective biocatalyst for MES, we need to improve its electron uptake ability and growth under photoelectroautotrophic conditions. Because TIE-1 interacts with various forms of iron while using it as a source of electrons for photoautotrophy (photoferroautotrophy), we tested the ability of iron-based redox mediators to enhance direct electron uptake. Our data show that soluble iron cannot …


Proteasome Storage Granules Protect Proteasomes From Autophagic Degradation Upon Carbon Starvation, Richard S. Marshall, Richard D. Vierstra Apr 2018

Proteasome Storage Granules Protect Proteasomes From Autophagic Degradation Upon Carbon Starvation, Richard S. Marshall, Richard D. Vierstra

Biology Faculty Research

26S proteasome abundance is tightly regulated at multiple levels, including the elimination of excess or inactive particles by autophagy. In yeast, this proteaphagy occurs upon nitrogen starvation but not carbon starvation, which instead stimulates the rapid sequestration of proteasomes into cytoplasmic puncta termed proteasome storage granules (PSGs). Here, we show that PSGs help protect proteasomes from autophagic degradation. Both the core protease and regulatory particle sub-complexes are sequestered separately into PSGs via pathways dependent on the accessory proteins Blm10 and Spg5, respectively. Modulating PSG formation, either by perturbing cellular energy status or pH, or by genetically eliminating factors required for …


Kelch F-Box Protein Positively Influences Arabidopsis Seed Germination By Targeting Phytochrome-Interacting Factor1, Manoj Majee, Santosh Kumar, Praveen Kumar Kathare, Shuiqin Wu, Derek Gingerich, Nihar R. Nayak, Louai Salaita, Randy Dinkins, Kathleen Martin, Michael Goodin, Lynnette M A Dirk, Taylor D. Lloyd, Ling Zhu, Joseph Chappell, Arthur G. Hunt, Richard D. Vierstra, Enamul Huq, A Bruce Downie Apr 2018

Kelch F-Box Protein Positively Influences Arabidopsis Seed Germination By Targeting Phytochrome-Interacting Factor1, Manoj Majee, Santosh Kumar, Praveen Kumar Kathare, Shuiqin Wu, Derek Gingerich, Nihar R. Nayak, Louai Salaita, Randy Dinkins, Kathleen Martin, Michael Goodin, Lynnette M A Dirk, Taylor D. Lloyd, Ling Zhu, Joseph Chappell, Arthur G. Hunt, Richard D. Vierstra, Enamul Huq, A Bruce Downie

Biology Faculty Research

Seeds employ sensory systems that assess various environmental cues over time to maximize the successful transition from embryo to seedling. Here we show that the Arabidopsis F-BOX protein COLD TEMPERATURE-GERMINATING (CTG)-10, identified by activation tagging, is a positive regulator of this process. When overexpressed (OE), CTG10 hastens aspects of seed germination. CTG10 is expressed predominantly in the hypocotyl, and the protein is localized to the nucleus. CTG10 interacts with PHYTOCHROME-INTERACTING FACTOR 1 (PIF1) and helps regulate its abundance in planta. CTG10-OE accelerates the loss of PIF1 in light, increasing germination efficiency, while PIF1-OE lines fail to complete germination in …


The Life Of A Microtubule, Ram Dixit, Sabine Petry Mar 2018

The Life Of A Microtubule, Ram Dixit, Sabine Petry

Biology Faculty Research

The Minisymposium “The Life of a Microtubule: Birth, Dynamics and Function” highlighted new findings on how microtubules (MTs) are made, how their length and spatial organization is regulated, and finally how they contribute to cellular functions.


Overdispersed Spatial Patterning Of Dominant Bunchgrasses In Southeastern Pine Savannas, Katherines A. Hovanes, Kyle E. Harms, Paul R. Gagnon, Jonathan A. Myers, Bret D. Elderd Feb 2018

Overdispersed Spatial Patterning Of Dominant Bunchgrasses In Southeastern Pine Savannas, Katherines A. Hovanes, Kyle E. Harms, Paul R. Gagnon, Jonathan A. Myers, Bret D. Elderd

Biology Faculty Research

Spatial patterning is a key natural history attribute of sessile organisms that frequently emerges from and dictates potential for interactions among organisms. We tested whether bunchgrasses, the dominant plant functional group in longleaf pine savanna groundcover communities, are nonrandomly patterned by characterizing the spatial dispersion of three bunchgrass species across six sites in Louisiana and Florida. We mapped bunchgrass tussocks of >5.0 cm basal diameter in three [Formula: see text] plots at each site. We modeled tussocks as two-dimensional objects to analyze their spatial relationships while preserving sizes and shapes of individual tussocks. Tussocks were overdispersed (more regularly spaced than …


New Classification Of The Dictyostelids, Sanea Sheikh, Mats Thulin, James C. Cavender, Ricardo Escalante, Shin-Ichi Kawakami, Carlos Lado, John C. Landolt, Vidyanand Nanjundiah, David C. Queller, Joan E. Strassmann, Frederick W. Spiegel, Steven L. Stephenson, Eduardo M. Vadell, Sandra L. Baldauf Feb 2018

New Classification Of The Dictyostelids, Sanea Sheikh, Mats Thulin, James C. Cavender, Ricardo Escalante, Shin-Ichi Kawakami, Carlos Lado, John C. Landolt, Vidyanand Nanjundiah, David C. Queller, Joan E. Strassmann, Frederick W. Spiegel, Steven L. Stephenson, Eduardo M. Vadell, Sandra L. Baldauf

Biology Faculty Research

Traditional morphology-based taxonomy of dictyostelids is rejected by molecular phylogeny. A new classification is presented based on monophyletic entities with consistent and strong molecular phylogenetic support and that are, as far as possible, morphologically recognizable. All newly named clades are diagnosed with small subunit ribosomal RNA (18S rRNA) sequence signatures plus morphological synapomorphies where possible. The two major molecular clades are given the rank of order, as Acytosteliales ord. nov. and Dictyosteliales. The two major clades within each of these orders are recognized and given the rank of family as, respectively, Acytosteliaceae and Cavenderiaceae fam. nov. in Acytosteliales, and Dictyosteliaceae …


Elucidating A Role For The Cytoplasmic Domain In The Mycobacterium Tuberculosis Mechanosensitive Channel Of Large Conductance, Nadia Herrera, Grigory Maksaev, Elizabeth S. Haswell, Douglas C. Rees Jan 2018

Elucidating A Role For The Cytoplasmic Domain In The Mycobacterium Tuberculosis Mechanosensitive Channel Of Large Conductance, Nadia Herrera, Grigory Maksaev, Elizabeth S. Haswell, Douglas C. Rees

All Faculty Publications

Microbial survival in dynamic environments requires the ability to successfully respond to abrupt changes in osmolarity. The mechanosensitive channel of large conductance (MscL) is a ubiquitous channel that facilitates the survival of bacteria and archaea under severe osmotic downshock conditions by relieving excess turgor pressure in response to increased membrane tension. A prominent structural feature of MscL, the cytoplasmic C-terminal domain, has been suggested to infuence channel assembly and function. In this report, we describe the X-ray crystal structure and electrophysiological properties of a C-terminal domain truncation of the Mycobacterium tuberculosis MscL (MtMscLΔC). A crystal structure of MtMscLΔC solubilized in …


Draft Genome Sequence Of Streptomyces Sp. Strain Jv178, A Producer Of Clifednamide-Type Polycyclic Tetramate Macrolactams, Yunci Qi, John M. D’Alessandro, Joshua A.V Blodgett Jan 2018

Draft Genome Sequence Of Streptomyces Sp. Strain Jv178, A Producer Of Clifednamide-Type Polycyclic Tetramate Macrolactams, Yunci Qi, John M. D’Alessandro, Joshua A.V Blodgett

Biology Faculty Research

Here, we report the draft genome sequence of Streptomyces sp. JV178, a strain originating from Connecticut (USA) garden soil. This strain produces the polycyclic tetramate macrolactam compounds clifednamides A and B. The draft genome contains 10.65 Mb, 9,045 predicted protein coding sequences, and several natural product biosynthetic loci.


Understanding The Paradox Of Genetic Diversity In Uropathogenic E. Coli: The Uncommon Evolution Of A Common Pathogen, Henry Louis Schreiber Dec 2017

Understanding The Paradox Of Genetic Diversity In Uropathogenic E. Coli: The Uncommon Evolution Of A Common Pathogen, Henry Louis Schreiber

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are the second most common bacterial infection of people in the U.S.A and are frequently recurrent, as an initial UTI is quickly followed by a second episode in 30-35% of cases despite appropriate antibiotic treatment and clearance of the bacteria from the urine. The vast majority, >80%, of UTIs are caused by uropathogenic Escherichia coli (UPEC). UPEC that colonize the bladder are thought to originate in the gut, where they live as commensal organisms. UPEC can be shed in feces to colonize the vagina and/or periurethral area, and then can ascend into the bladder to start …


Knowledge Driven Approaches And Machine Learning Improve The Identification Of Clinically Relevant Somatic Mutations In Cancer Genomics, Benjamin John Ainscough Dec 2017

Knowledge Driven Approaches And Machine Learning Improve The Identification Of Clinically Relevant Somatic Mutations In Cancer Genomics, Benjamin John Ainscough

Arts & Sciences Graduate Student Theses and Dissertations

For cancer genomics to fully expand its utility from research discovery to clinical adoption, somatic variant detection pipelines must be optimized and standardized to ensure identification of clinically relevant mutations and to reduce laborious and error-prone post-processing steps. To address the need for improved catalogues of clinically and biologically important somatic mutations, we developed DoCM, a Database of Curated Mutations in Cancer (http://docm.info), as described in Chapter 2. DoCM is an open source, openly licensed resource to enable the cancer research community to aggregate, store and track biologically and clinically important cancer variants. DoCM is currently comprised of 1,364 variants …


Roles Of Peroxisomes And Peroxisome-Derived Products In Controlling Plant Growth And Stress Responses, Elizabeth May Frick Dec 2017

Roles Of Peroxisomes And Peroxisome-Derived Products In Controlling Plant Growth And Stress Responses, Elizabeth May Frick

Arts & Sciences Graduate Student Theses and Dissertations

The peroxisome is a vital organelle conserved through the entire eukaryotic lineage. In all examined species, peroxisomes are responsible for such essential processes as fatty acid beta-oxidation and metabolism of reactive oxygen species (ROS). In plants, peroxisomes have taken on additional specialized roles, such as production of some plant hormones and vitamins. In this work, I have uncovered novel factors regulating peroxisome number in model species Arabidopsis thaliana, and novel mechanisms governing how peroxisomes respond to salt stress. I discovered a role for Arabidopsis MAP KINASE17 (MPK17) as a negative regulator of peroxisome division that acts in the salt-stress response …


A Generalized Biophysical Model Of Transcription Factor Binding Specificity And Its Application On High-Throughput Selex Data, Shuxiang Ruan Dec 2017

A Generalized Biophysical Model Of Transcription Factor Binding Specificity And Its Application On High-Throughput Selex Data, Shuxiang Ruan

Arts & Sciences Graduate Student Theses and Dissertations

The interaction between transcription factors (TFs) and DNA plays an important role in gene expression regulation. In the past, experiments on protein–DNA interactions could only identify a handful of sequences that a TF binds with high affinities. In recent years, several high-throughput experimental techniques, such as high-throughput SELEX (HT-SELEX), protein-binding microarrays (PBMs) and ChIP-seq, have been developed to estimate the relative binding affinities of large numbers of DNA sequences both in vitro and in vivo. The large volume of data generated by these techniques proved to be a challenge and prompted the development of novel motif discovery algorithms. These algorithms …


Longitudinal Cerebrospinal Fluid Biomarkers Of Alzheimer Disease: Movement Toward The Diagnosis, Prognosis And Staging Of Disease, Courtney Sutphen Dec 2017

Longitudinal Cerebrospinal Fluid Biomarkers Of Alzheimer Disease: Movement Toward The Diagnosis, Prognosis And Staging Of Disease, Courtney Sutphen

Arts & Sciences Graduate Student Theses and Dissertations

Alzheimer’s disease (AD) is a devastating neurodegenerative disease that slowly claims the memories and experiences that comprise the life experiences of individuals that suffer from the disease. Despite a continually accelerating pace of research and discovery, a viable therapeutic intervention for AD has yet to be realized. There are a multitude of factors that may contribute to this difficulty including the challenge of separating the overall disease of Alzheimer’s from the clinically recognizable memory loss that occurs in what is now known to be the end-stage of the disease. Efforts to treat AD have increasingly turned toward very early disease …


Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell Dec 2017

Regulation Of Gene Expression By Rna Binding Proteins And Micrornas, Kyle Cottrell

Arts & Sciences Graduate Student Theses and Dissertations

Regulation of gene expression is essential to life. Post-transcriptional regulation of gene expression is a complex process with many inputs that lead to changes in localization, translation and stability of mRNAs. The translation and stability of many mRNAs is regulated by cis-elements, such as mRNA-structure or codon optimality; and by trans-acting factors such as RBPs and miRNAs. Here I report on the complex interactions between RBPs, miRNAs and characteristics of their target mRNAs in respect to effects on translation and RNA stability.Using a reporter based approach we studied modulation of microRNA-mediated repression by various mRNA characteristics. We observed the influence …