Life Sciences Commons^™

Impairment Of The Glial Phagolysosomal System Drives Prion-Like Propagation Of Huntington’S Disease, Graham Davis

Theses and Dissertations

The ability of glia to tightly regulate neuronal health and homeostasis in the CNS is conserved across species. Yet, despite the ability to degrade protein aggregates, glia are vulnerable to the accumulation of neurotoxic amyloid aggregates during neurodegenerative disease progress, and even exacerbate their spread. A developing narrative highlights glia as a double-edged sword in neurodegenerative diseases: initially capable of dynamically responding to amyloid aggregate-ladened dying neurons but also capable of inducing chronic inflammation and creating seeding-competent amyloid oligomers. Thus, uncovering the mechanisms that allow glia to control aggregate deposition while preventing the neurotoxic effects and seed generation is vital …

Dissecting Dystrophin's Roles, Subcellular Organization, And Functional Network In Drosophila Oogenesis, Mina Amini Moghaddam

Theses and Dissertations

Mutations in the giant actin-membrane linker protein Dystrophin (Dys) are the cause of Duchenne Muscular Dystrophy (DMD). In the Drosophila model system, the highly conserved Dys protein is not required for viability but is required for proper wing and ovarian development. Dys mutations produce two visible phenotypes: posterior crossveins are detached from the longitudinal veins, and in oogenesis the developing eggs fail to elongate properly. This provides an opportunity to explore the less-understood cellular and developmental roles of Dys and gain a new insight into how tissues adopt their correct shapes.

Animals from worms to flies to humans express multiple …

Mef2-Bound Genes May Influence Ethanol Sedation In Drosophila Melanogaster, Katlyn M. Myers

Theses and Dissertations

Alcohol Use Disorder (AUD) is a global health issue that affects millions of people every year. This disorder has serious negative mental and physical consequences. Currently, treatment options for this disorder are largely limited to psychological therapy, with very few medications available to treat it. Being able to identify the environmental and genetic components that influence AUD can help improve diagnosis and treatment options. Previous studies in humans have shown a link between initial sensitivity and risk for alcohol abuse. Our laboratory uses Drosophila melanogaster as a model to study the genetic and environmental components of alcohol-related behaviors. Previous lab …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Genetic And Environmental Factors Influence Drosophila Ethanol Sedation, Rebecca E. Schmitt

Theses and Dissertations

Alcohol use disorder is a global health issue that affects a significant portion of the population, with affects including both negative mental and physical consequences. Currently, there are few treatment options available to those who suffer from alcohol use disorder, alcohol abuse, or alcohol dependence. Identifying candidate genes or environmental influences would therefore improve the means for possible treatments or identification of those people at risk for alcohol use disorder. Previous studies in humans have demonstrated an inverse association between initial sensitivity and risk for alcohol abuse. This connection allows investigators, and our laboratory, to investigate genetic and environmental factors …

Acetobacter Fabarum Genes Influencing Drosophila Melanogaster Phenotypes, Kylie Makay White

Theses and Dissertations

Research in our lab has predicted hundreds of bacterial genes that influence nine different traits in the fruit fly, Drosophila melanogaster. As a practical alternative to creating site-directed mutants for each of the predicted genes, we created an arrayed transposon insertion library using a strain of Acetobacter fabarum DsW_054 isolated from fruit flies. Creation of the Acetobacter fabarum DsW_054 gene knock-out library was done through random transposon insertion, combinatorial mapping and Illumina sequencing. Successful mapping of transposon insertion was achieved for 6418 mutants with hits within 63% of annotated genes within Acetobacter fabarum DsW_054. Insertion sites were verified in …

Differential Expression Of Snmps And Their Underlying Transcriptional Regulation In Chemosensory Pathways Of Drosophila, Richard A. Fandino

Theses and Dissertations

Insects possess complex and diverse chemosensory pathways which have specific phenotypes determined by the regulated expression of specific combinations of genes. While many of these genes (e.g. ORs and GRs) have very narrow expression patterns, associating with only a limited number of chemosensory sensilla, SNMPs show a very broad expression pattern. In Drosophila, SNMP1 and SNMP2 associate with the majority of olfactory and gustatory sensilla, but express in different cell types. In olfactory sensilla, SNMP1 and SNMP2 associate with trichoid or coeloconic neurons respectively, and both additionally express in a variety of sensilla support cells; in gustatory sensilla, SNMP2 expresses …

Multi-Species Gene Networks And Drosophila Ethanol Sedation, Arnavaz Kollah

Theses and Dissertations

Alcohol use disorders (AUDs) are major health issues with few known genetic explanations. This project used the fruit fly (Drosophila melanogaster) model to identify genes and gene networks that influence alcohol intoxication, a phenotype related to alcohol abuse in humans. We used bioinformatic tools to build gene networks based on 24 published Drosophila ethanol-responsive genes with human orthologs. We then assessed the role of these networks in ethanol sedation by testing two of the networks seeded on IP3K2, a gene that regulates calcium signaling, and CG14630, a gene involved in carnitine biosynthesis. We knocked down several genes in each of …

The Effects Of Snmp-2 Gene Expression On Mating Discrimination In Male Drosophila Melanogaster, Kristen Taylor Ashourian

Theses and Dissertations

In order to distinguish between relevant and extraneous stimuli, insects have adapted specialized processes to perceive cues that are beneficial for survival and proliferation. Volatile molecules in the environment can stimulate olfactory receptors (ORs) and gustatory receptors (GRs) in chemosensory organs called sensilla. Specialized proteins located within these sensilla guide and assist chemosensory molecules to the receptors, which then trigger a transduction pathway that elicits behavioral responses. Sensory Neuron Membrane Proteins (SNMPs) are transmembrane proteins found on both gustatory and olfactory sensory organs in insects. There are two forms of these proteins, SNMP-1 and SNMP-2. InDrosophila melanogaster, the function of …

Network Analysis And Comparative Phylogenomics Of Micrornas And Their Respective Messenger Rna Targets Using Twelve Drosophila Species, M Ryan Woodcock

Theses and Dissertations

MicroRNAs represent a special class of small (~21–25 nucleotides) non-coding RNA molecules which exert powerful post-transcriptional control over gene expression in eukaryotes. Indeed microRNAs likely represent the most abundant class of regulators in animal gene regulatory networks. This study describes the recovery and network analyses of a suite of homologous microRNA targets recovered through two different prediction methods for whole gene regions across twelve Drosophila species. Phylogenetic criteria under an accepted tree topology were used as a reference frame to 1) make inference into microRNA-target predictions, 2) study mathematical properties of microRNA-gene regulatory networks, 3) and conduct novel phylogenetic analyses …