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Engineering Natural Competence Into The Fast-Growing Cyanobacterium Synechococcus Elongatus Utex 2973, Kristen Elizabeth Wendt Aug 2020

Engineering Natural Competence Into The Fast-Growing Cyanobacterium Synechococcus Elongatus Utex 2973, Kristen Elizabeth Wendt

Arts & Sciences Electronic Theses and Dissertations

Synechococcus elongatus UTEX 2973 is the fastest growing cyanobacterium discovered to date. Using water, carbon dioxide, and light alone, this organism can double in 1.5 hours under optimal conditions. The accelerated doubling exhibited by Synechococcus 2973 makes it a prime candidate to serve as a model photoautotrophic system. However, Synechococcus 2973 lacks one highly desirable feature: it cannot undergo natural transformation. This thesis seeks to engineer this capacity into this fast-growing system in order to create an organism that is both fast growing and naturally competent. Synechococcus 2973 is a unique platform because it is >99% genetically identical to another …


Genetic And Functional Characterization Of Novel Host Factors Regulating Virus Infection In Caenorhabditis Elegans, Luis Enrique Sandoval Aug 2020

Genetic And Functional Characterization Of Novel Host Factors Regulating Virus Infection In Caenorhabditis Elegans, Luis Enrique Sandoval

Arts & Sciences Electronic Theses and Dissertations

Viruses infect the majority of eukaryotic life on the planet and remain a global threat to human health. These pathogens are constrained to intracellular life cycles, as they exploit and rely on host factors and machinery throughout their entire reproduction process. While many of these viral life cycle factors have been reported and studied, our knowledge in the identity and function of these factors remains incomplete and a challenge in fundamental virology and the development of antiviral therapeutics. Caenorhabditis elegans offers an innovative approach for discovering novel host factors required for virus infection in a multicellular and simple model organism. …


Microrna Gene Expression States Underlying Individual Variation In Aging And Lifespan In Isogenic C. Elegans, Holly Kinser Aug 2020

Microrna Gene Expression States Underlying Individual Variation In Aging And Lifespan In Isogenic C. Elegans, Holly Kinser

McKelvey School of Engineering Theses & Dissertations

Average lifespan differs greatly between species, but lifespan among same-species individuals is also highly variable. While much effort has been devoted to uncovering longevity-associated traits and lifespan-extending perturbations in humans and model organisms, how differences in lifespan arise between individuals is unknown. Studies of human identical twins demonstrate that surprisingly little of the variation in lifespan between individuals can be explained by genetics and shared environment. Furthermore, even genetically identical C. elegans reared in highly homogeneous environments display a degree of variability in lifespan similar to that of outbred human populations. Thus, longevity must be determined at least in part …


The Good, The Brown, And The Healthy: Understanding Non-Thermogenic Brown Adipose Function In Obese Mice, Caryn Nicole Carson Aug 2020

The Good, The Brown, And The Healthy: Understanding Non-Thermogenic Brown Adipose Function In Obese Mice, Caryn Nicole Carson

Arts & Sciences Electronic Theses and Dissertations

Genetic and environmental factors heavily intertwine to affect metabolic homeostasis. To tease out the exact interactions between these two realms of influence, researchers often compare how one or multiple different inbred mouse strains react to various diets. An observation consistently seen across multiple strains on the same diet can reasonably be considered a general dietary effect, whereas an observation seen only in one strain of mice is more likely to result from a genetic cause or gene-by-environment interaction. Similarly to humans, a high fat diet causes many mouse strains to develop obesity and poor metabolic health, with varying degrees of …


Developing Tools For Identifying Tissue-Specific Epigenetic Marks And Predicting Dna Hydroxy/Methylation, Yu He May 2020

Developing Tools For Identifying Tissue-Specific Epigenetic Marks And Predicting Dna Hydroxy/Methylation, Yu He

Arts & Sciences Electronic Theses and Dissertations

A single genome can derive phenotypically unique cell types through various epigenetic modifications that instruct specific gene expression patterns. Histone modifications, DNA methylation, and DNA hydroxymetylation are the most common epigenetic modifications. To understand the mechanisms how these epigenetic modifications regulate gene expression, one often needs to map these marks genome-wide through profiling methods. Firstly, for histone modifications, Roadmap Epigenomics Consortium generated The Human Reference Epigenome Map, containing thousands of genome-wide histone modification datasets that describe epigenomes of a variety of different human tissue and cell types. This map has allowed investigators to obtain a much deeper and more comprehensive …


Pathophysiology And Treatment Of Murine Globoid Cell Leukodystrophy, Yedda Li May 2020

Pathophysiology And Treatment Of Murine Globoid Cell Leukodystrophy, Yedda Li

Arts & Sciences Electronic Theses and Dissertations

Infantile globoid cell leukodystrophy (GLD, Krabbe disease) is a rapidly progressing, invariably fatal pediatric disorder first described in 1916. Krabbe disease is caused by a deficiency in the lysosomal enzyme, galactosylceramidase (GALC), and is characterized clinically by failure to thrive, limb stiffness, seizures, developmental regression, and death by 2-4 years of age. Galactosylceramidase degrades the cytotoxic glycolipid, galactosylsphingosine (psychosine). In the absence of GALC activity, psychosine accumulates primarily in oligodendrocytes and Schwann cells, resulting in profound demyelination. In 1972, psychosine was hypothesized to be responsible for the clinical signs associated with Krabbe disease. However, the ‘Psychosine Hypothesis’ has never been …


Transcription Factor-Mediated Epigenetic Regulation In The Healthy Brain And Neurological Disease, Alexander J. Cammack May 2020

Transcription Factor-Mediated Epigenetic Regulation In The Healthy Brain And Neurological Disease, Alexander J. Cammack

Arts & Sciences Electronic Theses and Dissertations

Proper cellular development and function is a complex process established by elaborate gene expression networks. These networks are regulated by epigenetic processes, which alter chromatin states and coordinate the binding of transcription factors (TFs) to regulatory elements (REs), such as enhancers, across the genome to facilitate gene expression. It follows then that a major experimental effort is to profile and understand the binding patterns of TFs to REs in various cellular types and contexts. Critically however, current TF profiling techniques are limited in their abilities to profile TF occupancy in targeted cellular populations and temporal windows, hindering investigations into epigenetic …


Dendritic Cell Development And Function, Vivek Durai May 2020

Dendritic Cell Development And Function, Vivek Durai

Arts & Sciences Electronic Theses and Dissertations

Dendritic cells (DCs) are a group of immune cells that include both classical dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). cDCs are further comprised of two distinct subsets, cDC1s and cDC2s, which play critical roles in the initiation of innate and adaptive immune responses. Understanding how these lineages develop and function is therefore paramount. All DCs require the receptor tyrosine kinase Flt3 and its ligand Flt3L for their development, but the loss of Flt3L in mice leads to a more severe DC deficiency than does the loss of Flt3. This has led to speculation that Flt3L can bind to …


Multi-Omics Integration For Gene Fusion Discovery And Somatic Mutation Haplotyping In Cancer, Steven Mason Foltz May 2020

Multi-Omics Integration For Gene Fusion Discovery And Somatic Mutation Haplotyping In Cancer, Steven Mason Foltz

Arts & Sciences Electronic Theses and Dissertations

Cancer is a disease caused by changes to the genome and dysregulation of gene expression. Among many types of mutations, including point mutations, small insertions and deletions, large scale structural variants, and copy number changes, gene fusions are another category of genomic and transcriptomic alteration that can lead to cancer and which can serve as therapeutic targets. We studied gene fusion events using data from The Cancer Genome Atlas, including over 9,000 patients from 33 cancer types, finding patterns of gene fusion events and dysregulation of gene expression within and across cancer types. With data from the CoMMpass study (Multiple …


Genetic Interactions And Maternal Genes Modulate Congenital Heart Disease Risk, Ehiole Ogboma Akhirome May 2020

Genetic Interactions And Maternal Genes Modulate Congenital Heart Disease Risk, Ehiole Ogboma Akhirome

Arts & Sciences Electronic Theses and Dissertations

Congenital heart disease (CHD) is the most common congenital anomaly, which makes it a leading cause of infant mortality. Congenital heart defects are a cluster of distinct developmental malformations that affect the vasculature, musculature and organization of the heart, each with varying clinical severity. Although medical and surgical advances have reduced CHD mortality in newborns and children, these patients grow up and many experience serious morbidity and early mortality. The first step toward reducing this burden is to understand the causes of CHD. Surprisingly, environmental insults and de novo mutations are estimated to explain less than one-third of CHD cases. …


Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Naveen C. Reddy May 2020

Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Naveen C. Reddy

Arts & Sciences Electronic Theses and Dissertations

Precise control of gene expression is essential for neural development and function. This control is regulated by the interplay of chromatin remodelers and transcription factors (TFs). To better understand these mechanisms involved in gene regulation, we pursue two questions: 1) what are the roles of the chromatin remodeler CHD7 in cerebellar development and 2) what are the roles of the MEF2 TF family in cerebellar function. CHD7 mutations are causative for CHARGE syndrome, a heterogeneous disorder affecting many organ systems, occurring in 1:10,000 newborns. Recent MRI studies have identified cerebellar hypoplasia and foliation defects in a large portion of CHARGE …


Epigenetic Dynamics In Normal And Disease Models, Hyo Sik Jang May 2020

Epigenetic Dynamics In Normal And Disease Models, Hyo Sik Jang

Arts & Sciences Electronic Theses and Dissertations

Deciphering how epigenetic factors, such as DNA methylation and chromatin accessibility, shape normal development and disease progression has been an outstanding goal in developmental biology. Here, I present multiple branches of my thesis to elucidate the epigenetic controls that direct aging in brain, regulate cell fate decision of zebrafish iridophore in pigment differentiation, and dysregulate transposable elements (TEs) in cancer. The first branch focuses on benchmarking a computational statistic tool to characterize DNA methylation dynamics of aging in mouse prefrontal cortex by combining WGBS and TAB-seq to dissect the contribution of CpG methylation and hydroxymethylation. For the second branch, we …


Fgf20 In Olfactory System And Cochlea Development, Lu Morgan Yang May 2020

Fgf20 In Olfactory System And Cochlea Development, Lu Morgan Yang

Arts & Sciences Electronic Theses and Dissertations

The olfactory epithelium (OE) is a neurosensory organ required for the sense of smell. Turbinates, bony projections from the nasal cavity wall, increase the surface area within the nasal cavity lined by the OE. We identified a population of OE progenitor cells that expand horizontally during development to populate all lineages of the mature OE and increase OE surface area. We show that these Fgf20-positive, epithelium-spanning progenitor (FEP) cells are responsive to Wnt/β-Catenin signaling. Wnt signaling suppresses FEP cell differentiation into OE basal progenitors and their progeny, and positively regulates Fgf20 expression. We further show that FGF20 signals to the …