Biology 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 …

Characterization Of The Immune Deficiency Pathway During Female Meiosis In Drosophila Melanogaster, Sarah Mashburn

College of Science and Health Theses and Dissertations

Organisms can defend against pathogens by significantly increasing the diversity of their progeny, so that some progeny are more likely to survive infection. This led to the prediction that infection should cause an increase in recombination rates which was seen in a previous study. However, the mechanism that regulates recombination rates in response to infection is not understood and in that study they did not provide a mechanism for how that can occur. In an RNAi screen, our lab found the gene mustard (mtd) is required for normal recombination rates. This gene was previously shown to be part of the …

Effects Of Actin-Destabilizing Drugs On Motor Function In Drosophila Melanogaster, Caden Sullivan

Honors Theses

Actin dynamics influence many cellular processes including neural connectivity and function. One way to better understand and study the regulation of these dynamics is to manipulate actin dynamics and observe the effects in motor function as a proxy to changes on the neuromuscular junctions in developing neural tissue. On that line, this investigation hypothesized that changing the actin dynamics during development via drug manipulation results in observable effects in locomotion. One of the common actin regulatory drugs used throughout the literature includes Latrunculin A, which was used in this study. Methods included applying this actin destabilizing drug on developing wildtype …

The Role Of Cort And Anaphase Promoting Complex/Cyclosome (Apc/C) In Drosophila Sex Determination And Meiosis, Abuzar Sikander Malik

Electronic Theses and Dissertations

The E3 ubiquitin ligase, APC/C, is essential for the completion cell cycle; along with its co-activators it allows mitotic exit and maintenance of G1. APC/C marks various substrates with ubiquitin chains; marked substrates are subsequently destroyed via the 26S proteasome pathway. Cort is a Drosophila female meiosis specific activator of APC/C. Cort works within meiosis in conjunction with Fzy to mediate Securin and cyclin destruction. A C-terminal IR-tail motif and a N-terminal C-box support Cort-APC/C interaction, whereas short motifs like D-box and KEN-box on the target protein impart substrate recognition to Cort. Cort expression is tightly controlled in the female …

Drosophila Melanogaster As A Model For Male Reproductive System Ethanol Toxicity, Gbemisola Ilelaboye

Seton Hall University Dissertations and Theses (ETDs)

Drosophila melanogaster has been extensively used in different types of research as a model organism due to its high reproductivity, short life span, and easy maintenance. In this paper, we examined drosophila as a model for ethanol toxicity in the male reproductive system. We developed three assays: The DAPI assay, sperm viability assay, and tubulin staining assay. The DAPI assay is a nuclear staining assay that assesses the effects of various ethanol concentrations in late spermiogenesis in which increased detrimental effects to the sperm bundles were observed. The second assay consisted of the sperm viability assay which showed an increase …

Developing A Novel Place Preference Assay To Compare Drosophila Species Over Time, Martha M. Brinson

Honors Theses

Across phylogeny, integration of external factors, memory, and internal states of the organism dictate organismal behavior and mechanisms. The underlying genetic components can affect these behaviors such as in genomic changes arising from speciation. In this thesis, a new place preference assay was evaluated in the analysis and investigation of two species of Drosophila flies (D. melanogaster and D. simulans) to measure similarities and differences and their attraction to two different food substrates. Sleep and circadian measurements were also recorded during experimentation. The Drosophila Activity Monitor 5M (DAM5M) System and Sleep Circadian Analysis MATLAB Program (SCAMP) analysis were …

Translation Control Tunes Drosophila Oogenesis, Elliot T. Martin

Legacy Theses & Dissertations (2009 - 2024)

The decision of a stem cell to either self-renew or differentiate is controlled by specific cellularpathways that can act at the level of transcription, translation, or post-translation. To study the regulation of these pathways in-vivo, I have used the female Drosophila germline as a model system. Each of the steps from germline stem cell (GSC) to egg require changes in cellular pathways. These changes can occur at the level of transcription, post-transciption, translation, or post-translation . Decades of research has elucidated many of the changes to gene that occur during oogenesis, however, many players in this process still remain mysterious. …

Development And Characterization Of A Tissue-Specific Reporter Line For Monitoring Circadian Clock Transcriptional Activity, Lilyan Mather

Master's Theses

Daily rhythms in physiology and behavior are produced by a circadian system consisting of a central clock located in the brain and peripheral clocks located in various peripheral tissues. Circadian clocks track time of day through the presence of a molecular clock that functions as a transcriptional-translational feedback loop. In the nucleus, the transcription factors CLOCK (CLK) and CYCLE (CYC) activate transcription of clock genes period (per) and timeless (tim). PER and TIM proteins slowly accumulate in the cytoplasm before entering the nucleus, where they inhibit CLK and CYC, and therefore repress their own transcription. Degradation of nuclear PER and …

The Importance Of Protein Context In Spinocerebellar Ataxia Type 3, Sean Luis Johnson

Wayne State University Dissertations

Spinocerebellar Ataxia Type 3 (SCA3) is a member of the family of polyglutamine (polyQ) neurodegenerative disorders that includes Huntington's Disease and several other SCAs. SCA3, the most common dominant ataxia in the world, is caused by polyQ tract expansion in the protein, ataxin-3. How SCA3 occurs and how to treat it remain unresolved issues. The primary culprit of toxicity in all polyQ diseases is the glutamine repeat: its abnormal expansion leads to neuronal dysfunction and death. With that said, there is indisputable evidence that the way polyQ-dependent toxicity presents—areas impacted, cellular processes perturbed—is predicated in large part on regions outside …

A Combinatorial 5-Htr Expression Pattern Within The Ventral Projection Neurons Of The D. Melanogaster Olfactory Circuit., Mohd Freezely Ezzani Bin Mazri

Graduate Theses, Dissertations, and Problem Reports

Neuromodulation allows neurons within a circuit to respond to stimuli from the environment according to the correct ecological value, context, and internal state of the animal. Serotonin (5-HT) is a neuromodulator that can generate different outcomes based on its target’s serotonin receptor (5-HTR) expression by affecting secondary messenger cascades. Within the Drosophila olfactory system, ventral projections neurons (vPN) express all five insect 5-HTR that project into two olfactory processing regions, the antennal lobe (AL) and the lateral horn (LH). The significance of this 5-HTR expression is unknown. In this study, I theorized the patterns of 5-HTR expression of vPNs. I …

A Forward Genetic Screen To Identify Human Genes Of Interest And Their Roles In Ovarian Cancer, Susan A. Ihejirika

Honors College Theses

Drosophila melanogaster, fruit flies, are very important for modeling and studying human diseases. This study identifies human genes of interest and their contributions to epithelial ovarian carcinogenesis and progression as well as the roles orthologs of these genes play in Drosophila melanogaster. This is important because ovarian cancer is the most common cause of death among the gynecological cancers. This identification of genes was carried out using a forward genetic screen employing the widely used GMR-Gal4 driver/UAS-transgene system. The GMR-Gal4 driver is commonly utilized to express transgenes in the developing eye of the fruit fly. Transgenes that are expressed using …

Rna Modification Landscape And Its Contribution To Egg Production, Ian Thomas Rapisarda

Legacy Theses & Dissertations (2009 - 2024)

Germline stem cells differentiate into mature egg or sperm cells that go through the process of fertilization which gives rise to all sexually reproducing organisms. During this process of differentiation, germ cells undergo a switch from mitosis to meiosis that allows for proper development and specification of the future gamete. The mechanisms that facilitate this shift from mitosis to meiosis, however, are not well understood. To gain insight into this process, we used Drosophila oogenesis as our model. To identify what RNA modifications are present during oogenesis we genetically enriched for each stage of development and performed mass spectrometry. We …

The Role Of The Dal Neurons In Modulating Circadian Rhythms In Olfactory Short-Term Memory In Drosophila Melanogaster, Cooper Ruwe

Honors Theses

Depressed short-term memory (STM) abilities during non-adaptive times of the day can significantly impact those who work occupations that require peak levels of cognitive functioning around the clock. While much work has gone into understanding the endogenous clock and circadian rhythms, there is still much to learn about the neural circuity that underlies the daily rhythms that define these regular oscillations in STM performance. The DAL neurons in the Drosophila brain are part of the circadian network and innervate the mushroom bodies (MBs), the species’ olfactory learning center, making them compelling candidates to be involved in circadian circuitry for olfactory …

Experimental Use Of Drosophila To Model Proliferation Of Sars-Cov-2 Infected Cells, Valerie Wicks

Undergraduate Honors College Theses 2016-

Drosophila have been vectors for scientific research since the beginning of the 20th century. Their successful use within experiments that investigated mendelian genetics inspired their continuous application to biological research. This includes topics that detailed what is now known as innate immunity. The innate immune system of Drosophila is a first line of defense against pathogens. Innate immunity has been extensively researched and has reserved responses between Drosophila and mammals. Specifically, Drosophila have been experimentally targeted to draw conclusions on human infecting viruses such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus (SARS-Cov-1). Such experiments modeled viral …

Describing A Putative Corollary Discharge Circuit In Drosophila, Kaitlyn Nicole Boone

Graduate Theses, Dissertations, and Problem Reports

Corollary discharge (CD) circuits provide critical information about movement and behavior to provide context to sensory processing. However, to date, there has not been a comprehensive study of CD circuits at a single-cell level. In this thesis, I aimed to resolve the connectivity of ascending histaminergic neurons, consisting of two pairs, the mesothoracic pair (MsAHNs) and metathoracic pair (MtAHNs) at a single-cell level and characterize contexts of activation. Using transgenic techniques, connectomics and transcriptomics, we identify neural populations receiving input from the AHNs and neural populations with significant output to the AHNs. We explored where the AHNs predominantly receive synaptic …

The Validation Of Predicted Biological Age Of Drosophila Melanogaster From Combined Statistical Modeling, Lauren Francis

Masters Theses

"Sleep is essential for maintaining a healthy body and mind and is associated with aging and aging related diseases. There are individual differences in fly as well as human sleep behavior and lifespan. Between and within individuals, sleep varies in characteristics including consolidation, rhythmicity, continuity, duration, and more. Various evidence in the literature suggests there are many molecular pathways involved with aging and they may be different for individuals. Our research is interested in a possible restorative mechanism of sleep and the ramifications of that mechanism to aging. We have developed two predictive models of aging using the fruit fly …

Structural Characterization Of The Novel Flightin Domain Wyr And Its Defining Role In The Thick Filament Structure And Mechanics, Lynda Menard

Graduate College Dissertations and Theses

The evolutionary success of Insecta has been attributed largely to the development of efficient means of motility: flight powered by muscle architecture harboring a largely conserved yet tunable system of power relay. The indirect flight muscle (IFM) of Drosophila melanogaster is a well-studied model for dissection of the structural and mechanical means by which muscle operates and evolves. Striated muscle, conserved throughout Animalia, is demarcated by an ordered array of thick- and thin-filaments prominently composed of the proteins myosin and actin. Flightin (fln) is a myosin binding thick filament protein essential for IFM stability, structure and function. The manner by …

Functional Genetic Approaches To Provide Evidence For The Role Of Toolkit Genes In The Evolution Of Complex Color Patterns In Drosophila Guttifera, Mujeeb Olushola Shittu

Dissertations, Master's Theses and Master's Reports

Toolkit genes are set of genes that orchestrate the development of basic body plan of animals, and they are highly conserved in all animals. The co-option of the toolkit genes into the pigmentation pathway has led to the evolution of novel species. This study focuses on understanding how the complex color patterns in animals develop by using the Drosophila species in the quinaria group as models. We developed an mRNA in situ hybridization (ISH) protocol, which allowed us to study gene expression patterns in the abdomen of developing pupae of non-model Drosophila species (Chapter 2). Through ISH, we found that …

Drosophila Model To Study Muscle Atrophy, Aaron Aghai

Master of Science in Integrative Biology Theses

Muscle atrophy (MA) is a phenomenon of muscle mass loss due to accelerated protein degradation in muscle fibers. Some pathological conditions, such as chronic inflammation or cancer, induce accelerated MA, which complicates medical treatment, hampers recovery of fragile patients, and ultimately can be the cause of a patient’s death. To gain better control over MA, more information is required about the whole spectrum of genetic factors that can influence MA.

Drosophila provides an excellent platform for genetic screening, although it has somewhat limited utility for MA research since insect muscles lack the level of plasticity found in mammalian muscles. We …

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 …

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

Direct Evidence Of Missing Mepsps Using Ca2-Sensor Imaging, Petar Gajic

Biological Sciences

Following an action potential in the presynaptic neuron there is evoked release of neurotransmitter into the synapse which activates ionotropic transmembrane receptors on the postsynaptic membrane that cause depolarizations in voltage that get recorded as excitatory postsynaptic potentials (EPSPs). In the absence of an action potential there is spontaneous release of neurotransmitter that postsynaptically gets recorded as miniature excitatory postsynaptic potentials (mEPSPs). According to the quantal hypothesis, postulated by Bernard Katz, the mEPSPs are allor- none changes in potential caused by a single quantum of neurotransmitter, which when added up create EPSPs. Following studies have found that these two modes …

Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon

Electronic Thesis and Dissertation Repository

Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming neurons of …

The Effect Of Ph On Synaptic Transmission At The Neuromuscular Junction In Drosophila Melanogaster, Catherine Elizabeth Stanley

Theses and Dissertations--Biology

Synaptic transmission is the main avenue of neuronal communication and can be affected by a multitude of factors, both intracellularly and extracellularly. The effects of pH changes on synaptic transmission have been studied for many years across many different models. Intracellular acidification at the presynaptic terminal is known to occur with increased neuronal activity and can also occur in pathological conditions. The effects of these pH alterations are therefore an important area of study. Here, intracellular acidification using either propionic acid or the ammonium chloride pre-pulse technique was examined for the effects on both spontaneous and evoked synaptic transmission at …

Actin Regulation And Furrow Dynamics During Early Drosophila Embryogenesis, Yi Xie

Electronic Theses and Dissertations

Drosophila embryogenesis starts with a single nucleus undergo 13 rounds of nuclear divisions called syncytial cycles. Staring at cycle 10 when nuclei migrate to the surface of the embryo, massive and dynamic cortical actin structures and cleavage furrow formations occur. How actin regulators coordinate into an organized network directing three-dimension actin structures in the developing organisms is an unsolved question. Here, I present an in-depth characterization of actin cap dynamics: the actin caps go through expansion, stabilization, elongation and fragmentation phases in each cycle. Arp2/3 is the major contributor to actin cap formation. The functions of 7 different actin and …

The Development Of Complex Abdominal Spot Patterns In Three Drosophila Species, William A. Dion

Dissertations, Master's Theses and Master's Reports

Complex color patterns like the spots on leopards and butterfly wings beg the question – how did these traits evolve? To understand the evolution of novel morphologies, we need to study the differences in morphogenesis between closely related species. Here, I examine and compare the development of complex abdominal spot patterns among three species of Drosophila closely related in evolutionary time. Through in situ hybridization, I have characterized the expression patterns of three pigmentation genes among the fruit fly species. Additionally, I have built upon previous work in our lab regarding the regulation of pigmentation by beginning to develop an …

Analysis Of The Temporal Patterning Of Notch Downstream Targets During Drosophila Melanogaster Egg Chamber Development, Molly A. Rowe

Honors College Theses

Living organisms require complex signaling interactions and proper regulation of these interactions to influence biological processes. Of these complex networks, one of the most distinguished is the Notch pathway. Dysregulation of this pathway often results in defects during organismal development and can be a causative mechanism for initiation and progression of cancer. Despite previous research entailing the importance of this signaling pathway and the organismal processes that it is involved in, less is known concerning the major Notch downstream targets, especially the onset and sequence in which they are modulated during normal development. As timing of regulation may be linked …

Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey

Biology ETDs

Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a …

The Effects Of A Ketone Body On Synaptic Transmission, Alexandra Elizabeth Stanback

Theses and Dissertations--Biology

The ketogenic diet is commonly used to control epilepsy, especially in cases when medications cannot. The diet typically consists of high fat, low carb, and adequate protein and produces a metabolite called acetoacetate. Seizure activity is characterized by glutamate excitotoxicity and therefore glutamate regulation is a point of research for control of these disorders. Acetoacetate is heavily implicated as the primary molecule responsible for decreasing glutamate in the synapse; it is believed that acetoacetate interferes with the transport of glutamate into the synaptic vesicles. The effects on synaptic transmission at glutamatergic synapses was studied in relation to the ketogenic diet …

The Role Of Dunc13 In Ethanol Tolerance, Yusuke Wachi

Electronic Theses and Dissertations

Although the effects of ethanol on presynaptic activity have been studied, the molecular mechanisms and the changes in gene expression which are responsible for inducing ethanol tolerance are unclear. Munc13-1 is an active-zone protein that is essential for presynaptic vesicle fusion. This protein interacts with vesicle fusion machinery at presynaptic active zones in the mammalian brain. The C1 domain of Munc13-1 binds diacylglycerol (DAG), which helps membrane localization of this protein and promotes vesicle fusion, facilitating synaptic vesicle release. Previously, it was shown that ethanol binds to the C1 domain of Munc13-1 in vitro at concentrations below 100 mM (Das …