Life Sciences Commons^™

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

Genetic Circadian Mosaics And The Clock Network’S Contributions To Sleep, Lukasz Widziszewski

Dissertations, Theses, and Capstone Projects

Circadian rhythms are physiological and behavioral changes which follow a 24-hour cycle. Drosophila Melanogaster’s circadian clock neuronal network (CCNN) has been identified and several subpopulations have been characterized based on previous studies; the classifications of subpopulations of neurons within the CCNN are based on a return of anticipatory locomotor activity preceding the two daily light transitions (Lights on = dawn/Lights off = dusk). The neurons responsible for the return of anticipatory morning locomotor activity have been referred to as the M-cells, the group of neurons known to rescue evening anticipatory locomotor activity have been termed the E-cells. In this …

Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment, Maria P. Fernand, Hannah L. Pettibone, Joseph T. Bogart, Casey J. Roell, Charles E. Davey, Ausra Pranevicius, Khang V. Huynh, Sara M. Lennox, Boyan Kostadinov, Orie T. Shafer

Publications and Research

Networks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons. …

A Micro-Optic Stalk (Muos) System To Model The Collective Migration Of Retinal Neuroblasts, Stephanie Zhang, Miles Markey, Caroline D. Pena, Tadmiri Venkatesh, Maribel Vasquez

Publications and Research

Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes …

Invertebrate Retinal Progenitors As Regenerative Models In A Microfluidic System, Caroline D. Pena, Stephanie Zhang, Robert Majeska, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insuffcient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to …

Egfr Polymorphisms In Drosophila Melanogaster, Stacie Chue, Neha Mehta, Samantha Poon, Heather Trazino

Publications and Research

No abstract provided.

Collective Chemotaxis Of Retinal Neural Cells From Drosophila Melanogaster In Controlled Microenvironments, Stephanie Zhang

Dissertations and Theses

More than 172 million people are influenced by a retinal disorder that stems from either age-related or developmental causes. Of those, 1.5 million people endure a developmental retinal disorder. In the developing retina, neural cells undergo a series of highly complicated differentiation and migration process. A main cause of these diseases is abnormal collective migration of neural progenitors hindering the retinogenesis process. However, our grasp of collective migration and signaling molecules, critical to the developing retina, is incompletely understood. Understanding the molecular mechanisms, such as the fibroblast growth factor pathway, that regulate glial and neuronal migration provides decisive insights in …

A Combined Computational Strategy Of Sequence And Structural Analysis Predicts The Existence Of A Functional Eicosanoid Pathway In Drosophila Melanogaster, Michael Scarpati

Dissertations, Theses, and Capstone Projects

With increased understanding of their roles in signal transduction and metabolism, eicosanoids have emerged as important players in human health and disease. Mammalian prostanoids and related lipid mediators perform varied functions in different tissues and organs. Synthesized through the oxygenation of C20 polyunsaturated fatty acids, mammalian eicosanoids are both pro- and anti-inflammatory. The physiological contexts in which eicosanoid family members act at the cellular level are not well understood. In this study, we examined whether the genome of Drosophila melanogaster, a powerful model for innate immunity and inflammation, codes for the enzymes required for eicosanoid biosynthesis. We report the …

Retrotransposons Are The Major Contributors To The Expansion Of The Drosophila Ananassae Muller F Element, Wilson Leung, Gerard Mcneil

Publications and Research

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (.18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors …

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 …

Comparative Modeling And Functional Characterization Of Two Enzymes Of The Cyclooxygenase Pathway In Drosophila Melanogaster, Yan Qi

Dissertations, Theses, and Capstone Projects

Eicosanoids are biologically active molecules oxygenated from twenty carbon polyunsaturated fatty acids. Natural eicosanoids exert potent biological effects in humans, and a great deal of pharmaceutical research has led to the discovery of compounds for selective inhibition of specific enzymes in eicosanoid biosynthesis. Coupled with different receptors, eicosanoids mediate various physiological and pathophysiological processes, including fever generation, pain response, vasoconstriction, vasodilation, platelet aggregation, platelet declumping, body temperature maintenance and sleep-wake cycle regulation. In mammals, the eicosanoid biosynthesis has three pathways: the cyclooxygenase (COX) pathway, the lipoxygenase (LOX) pathway and the epoxygenase pathway. The COX pathway synthesizes prostanoids, which are important …

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar

Publications and Research

Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markers—Rho1, Rac1 and E-cadherin (Ecad)—resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different …

Role Of Glia Subsets In Neurodegeneration And Life Span Reduction; Gain-Of-Function Phenotypes Following Glia Specific Overexpression Of Rap/Fzr, An Activator Of The Anaphase-Promoting Complex, Amandeep Kaur

Dissertations and Theses

No abstract provided.

Role Of Drosophila Rap/Fzr (Cdh1) In Retinal Axon Targeting And Its Interactions With Loco, Liprin-A And Ras, Marta Gronska

Dissertations and Theses

The development of the wild type Drosophila compound eye involves stereotypical targeting of photoreceptor axons to the specific layers of the optic ganglion, medulla and lamina, in the third instar larvae. To test the hypothesis that ubiquitin ligases play an important role during retinal axon targeting we have examined the patterns of axon targeting in the developing eye of the retina aberrant in pattern (rap/fzr) mutants. Rap/Fzr is a homolog of mammalian Cdh1, an activator of anaphase promoting complex (APC), an E3 ubiquitin ligase. Previous work has shown that Rap/Fzr is required in cell cycle regulation, glia differentiation and pattern …