Life Sciences Commons^™

Minibrain And Wings Apart Control Organ Growth And Tissue Patterning Through Downregulation Of Capicua, Liu Yang

Graduate Doctoral Dissertations

The regulation of organ growth is a fundamental aspect of developmental biology. My work uses Drosophila as a model system to understand how the various growth regulators are coordinated. The transcriptional repressor Capicua (Cic) controls tissue patterning and restricts organ growth, and has been recently implicated in several cancers and neurodegenerative diseases. Cic has emerged as a primary sensor of signaling downstream of the receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase (ERK) pathway, but how Cic activity is regulated in different cellular contexts remains poorly understood. In order to identify Cic regulators, I have used affinity purification/mass spectrometry (AP-MS) to study …

Genetic Mechanisms For The Maintenance Of Behavioral Mating Barriers In Drosophila, Kathleen M. Mortland

Arts & Sciences Electronic Theses and Dissertations

One of the most successful and diverse systems involved in the maintenance of behavioral barriers between closely related animal species is pheromonal communication. In the fruit fly, contact chemosensation input is especially important during sexual decision-making as it allows for the sensing of sex and species-specific non-volatile cuticular hydrocarbons (CHCs), which function as insect pheromones. However, how pheromonal systems support the maintenance of mating barriers is puzzling since any change in either pheromone ligands or their cognate receptors would carry a fitness cost, which should be eliminated by stabilizing selection. To resolve this evolutionary conundrum I hypothesized that pleiotropic genes …

Endogenous Small Interfering Rna: Insights Into Esirna Biogenesis And Their Precursors, Andrew White Harrington

Dissertations

Rarely in research is the path to an answer straightforward. Initial questions lead to more questions, many times doubling back to allow for greater insight into the original question. For example, discovery of interactions between previously unrelated pathways can lead to breakthroughs with regard to understanding of gene regulation. One such novel interaction and the subsequent discoveries this interaction spurred are discussed herein. Transposons, or “Jumping Genes” are mobile genetic elements found throughout all three major domains of life. Transposons comprise 44% of the human genome and possess the ability to move within the genome. This ability makes them an …

Functional Significance Of Branch Points In Mirtrons, Britton A. Strickland

Honors Theses

MicroRNAs are a heterogeneous group of small regulatory RNAs generated by many pathways. Mirtrons (miR) are a class of microRNAs produced by splicing, and some mirtrons contain a 3’ tail located downstream from the self-complementary hairpin. During RNA splicing, a loop-like “lariat” intermediate structure is created when the 5’ end of the RNA is attached to an adenine called the branch point. The goal of this project is to uncover the contribution of branch point location to the processing of tailed mirtrons into functional gene regulators. This project approaches this issue from two directions. First, branch points were identified by …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations & Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations & Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

Tnf Signaling During Tissue Damage-Induced Nociceptive Sensitization In Drosophila, Juyeon Jo

Dissertations & Theses (Open Access)

Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive sensitization in both Drosophila and vertebrates. In Drosophila larval model of nociceptive sensitization, UV irradiation in results in epidermal apoptosis and thermal allodynia. TNF/Eiger is produced from dying epidermal cells and acts its receptor in nociceptive sensory neurons to induce thermal allodynia. Inhibition of TNF signaling results in attenuation of nociceptive sensitization whereas epidermal apoptosis still occurs in the absence of TNF. Major gaps in this model are the precise relationship between apoptotic cell death and production of TNF/Eiger, downstream signaling mediators for TNFR/Wengen, and target genes that alter nociceptive …

Reproductive Arrest And Stress Resistance In Winter-Acclimated Drosophila Suzukii., Jantina Toxopeus, Ruth Jakobs, Laura V Ferguson, Tara D Gariepy, Brent J Sinclair

Biology Publications

Overwintering insects must survive the multiple-stress environment of winter, which includes low temperatures, reduced food and water availability, and cold-active pathogens. Many insects overwinter in diapause, a developmental arrest associated with high stress tolerance. Drosophila suzukii (Diptera: Drosophilidae), spotted wing drosophila, is an invasive agricultural pest worldwide. Its ability to overwinter and therefore establish in temperate regions could have severe implications for fruit crop industries. We demonstrate here that laboratory populations of Canadian D. suzukii larvae reared under short-day, low temperature, conditions develop into dark 'winter morph' adults similar to those reported globally from field captures, and observed by us …

Reverse Genetic Screening Of Innexin Gap Junction Proteins In Drosophila Neurons, Shannon P. Fox

Senior Honors Projects, 2010-2019

The reflexive response and perception of pain (nociception) is an evolutionarily conserved process in animals. Pain can be a major health concern and current treatments often prove insufficient, especially in regards to chronic pain. Greater understanding of the molecular processes underlying pain sensation could lead to new and more effective treatments. The aim of this study is to investigate the molecular mechanisms of cold nociception in Drosophila melanogaster. A specific subset of peripheral sensory neurons (Class III dendritic arborization (da) neurons), are implicated in Drosophila larvae’s response to noxious cold.

Previous literature has associated a family of gap junction protein, …

The Essential Oil Of Lippia Alba Affects Drosophila Behavior And Physiology, Jibin Manimala

Biological Sciences

Lippia alba (LA) is a flowering shrub native to Central and South America. Its essential oil has been used in herbal medicine as an anti-anxiety drug and in aquaculture; it is used to sedate fish during transport (Daniel 2014. Essential oils are derived from plants usually through steam distillation. They are labeled as “essential” because it contains the odor of the plant. Its physiological action is unknown. We use the fruitfly Drosophila melanogaster to further define its behavioral actions and determine its underlying physiological effects. We first tested whether Lippia alba produced had an anesthetic effect on the fruitfly. We …

Population Dynamics Based On Resource Availability & Founding Effects: Live & Computational Models, Samuel Potter, Rebecca M. Krall, Susan Mayo, Diane Johnson, Kimberly J. Zeidler-Watters, Robin L. Cooper

Biology Faculty Publications

With the looming global population crisis, it is more important now than ever that students understand what factors influence population dynamics. We present three learning modules with authentic, student-centered investigations that explore rates of population growth and the importance of resources. These interdisciplinary modules integrate biology, mathematics, and computer-literacy concepts aligned with the Next Generation Science Standards. The activities are appropriate for middle and high school science classes and for introductory college-level biology courses. The modules incorporate experimentation, data collection and analysis, drawing conclusions, and application of studied principles to explore factors affecting population dynamics in fruit flies. The variables …

Apical Testis Structure And The Effects Of Cadmium Treatment On Spermatogenesis In Drosophila, Paulina J. Cardaci

Seton Hall University Dissertations and Theses (ETDs)

The fruit fly Drosophila melanogaster is used extensively as a model for studying molecular, genetic and cellular aspects of human disease and physiology. Our lab has used D. melanogaster and related species to study the structure of the testis stem cell niche, as well as other aspects of spermatogenesis. We previously revealed a novel stem cell niche structure in D. pseudoobscura, a distant relative of D. melanogaster. The signaling center of the D. melanogaster stem cell niche has a well-characterized rosette arrangement of fasciclin-positive cells terms the “hub”. D. pseudoobscura, however, lacks a punctuate hub and instead displays a …

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …

Controlled Microfluidics To Examine Growth-Factor Induced Migration Of Neural Progenitors In The Drosophila Visual System, Cade Beck, Tanya Singh, Angela Farooqi, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

BACKGROUND:

The developing visual system in Drosophila melanogaster provides an excellent model with which to examine the effects of changing microenvironments on neural cell migration via microfluidics, because the combined experimental system enables direct genetic manipulation, in vivo observation, and in vitro imaging of cells, post-embryo. Exogenous signaling from ligands such as fibroblast growth factor (FGF) is well-known to control glia differentiation, cell migration, and axonal wrapping central to vision.

NEW METHOD:

The current study employs a microfluidic device to examine how controlled concentration gradient fields of FGF are able to regulate the migration of vision-critical glia cells with and …

Pi(4)P Promotes Phosphorylation And Conformational Change Of Smoothened Through Interaction With Its C-Terminal Tail, Kai Jiang, Yajuan Liu, Junkai Fan, Jie Zhang, Xiang-An Li, B. Mark Evers, Haining Zhu, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc-Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an …

Optogenetic Stimulation Of Drosophila Heart Rate At Different Temperatures And Ca2+ Concentrations, Yuechen Zhu, Henry Uradu, Zana R. Majeed, Robin L. Cooper

Biology Faculty Publications

Optogenetics is a revolutionary technique that enables noninvasive activation of electrically excitable cells. In mammals, heart rate has traditionally been modulated with pharmacological agents or direct stimulation of cardiac tissue with electrodes. However, implanted wires have been known to cause physical damage and damage from electrical currents. Here, we describe a proof of concept to optically drive cardiac function in a model organism, Drosophila melanogaster. We expressed the light sensitive channelrhodopsin protein ChR2.XXL in larval Drosophila hearts and examined light‐induced activation of cardiac tissue. After demonstrating optical stimulation of larval heart rate, the approach was tested at low temperature …

An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone …

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly …

Identification Of Lead-Sensitive Expression And Splicing Quantitative Trait Loci In Drosophila Melanogaster By Analysis Of Rna-Seq Data, Wen Qu

Wayne State University Dissertations

Lead exposure has long been one of the most important topics in global public health since it is a potent developmental neurotoxin. Here, we conducted an expression QTL (eQTLs) analysis, which is genome-wide association analysis of genetic variants with differential gene expression, in the male heads of 79 Drosophila melanogaster recombinant inbred lines originally from eight parental strains in the presence or absence of developmental exposure to 250 µM lead acetate. The aim was to study the effects of lead exposure on gene expression and identify the lead-responsive genes. After detecting 1,536 cis-eQTLs and 952 trans-eQTLs (1000 permutation threshold at …

Two-Photon Excitation Based Photochemistry And Neural Imaging, Kevin Andrew Hatch

Open Access Theses & Dissertations

Two-photon microscopy is a fluorescence imaging technique which provides distinct advantages in three-dimensional cellular and molecular imaging. The benefits of this technology may extend beyond imaging capabilities through exploitation of the quantum processes responsible for fluorescent events. This study utilized a two-photon microscope to investigate a synthetic photoreactive collagen peptidomimetic, which may serve as a potential material for tissue engineering using the techniques of two-photon photolysis and two-photon polymerization. The combination of these techniques could potentially be used to produce a scaffold for the vascularization of engineered three-dimensional tissues in vitro to address the current limitations of tissue engineering. Additionally, …

Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss, Andrew B. Nuss, Jason M. Meyer, Daniel E. Sonenshine, R. Michael Roe, Robert M. Waterhouse, David B. Sattelle, Jose De La Fuente, Jose M. Ribeiro, Karine Megy

Biological Sciences Faculty Publications

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ~57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle …

The Role Of Arp2/3 In Ring Canal Development In Drosophila Melanogaster, Marina Tipold

Undergraduate Honors Thesis Collection

Infertility and impaired fecundity affect 8.2 million women in the United States. Intercellular bridges are essential to the proper formation of germ cells in many organisms; therefore, learning more about how they are formed and regulated during the formation of sperm and eggs could provide insight into how defects in their structure can impact fertility. Intercellular bridges are actin-rich structures that connect developing germ cells to each other and allow the transfer of materials. I used the development of the fruit fly egg as a model system to study formation and regulation of intercellular bridges. Specifically, I investigated the role …

Effect Of Maternal Age On Offspring Social Behaviour In Drosophila Melanogaster, Shirley Long

2016 Undergraduate Awards

Aging can be defined as the natural and progressive decline in physiological functioning leading to increased risk for disease and death. Although the effects of age are well characterised, much less work has been done to study whether these detrimental changes can be transmitted to offspring. Advanced parental age has been correlated with higher incidence of neuropsychiatric disorders such as autism in children. As average maternal age increases in North America, it is becoming increasingly relevant to study the effects of maternal and paternal age on offspring social behaviour. We hypothesize that advanced maternal age in Drosophila melanogaster will affect …

Consequences Of Developmental Lead (Pb2+) Exposure On Reproductive Strategies In Drosophila, Elizabeth Kathleen Peterson

Legacy Theses & Dissertations (2009 - 2024)

Anthropogenic lead (Pb) pollution is ubiquitous in the environment and a risk factor for both human and wildlife health. Pb exposure has the potential to alter reproductive strategies with respect to mate choice and reproductive output. This could be especially deleterious if these changes disrupt adaptive behavioral and reproductive life history strategies. Therefore, the overall aim of this body of work was to examine the consequences of developmental Pb exposure on reproductive strategies, using Drosophila melanogaster as a model system. In all experiments, D. melanogaster were reared from egg stage to adulthood in either control or leaded medium and were …