Genetics and Genomics Commons^™

Characterization Of Pathological Tau Mutants, Charles J. Mcdonald

Dissertations, Theses, and Capstone Projects

Tau is a protein expressed exclusively in glia and neurons in the central nervous system and implicated in several neurogenerative diseases called “tauopathies”. Among all the tauopathies, one third is characterized by the presence of genetic mutations leading to the synthesis of tau proteins with single amino acid substitutions at specific locations and affecting protein function. While most of the initial studies have emphasize the functional role of tau as modulator of the axonal cytoskeleton, it has recently been well accepted that tau is also an intrinsically disordered protein that tends to form membraneless organelles called coacervates, due to a …

Effects Of The Otx2ecr2 Enhancer & Prox1 Overexpression In Murine Retina Development, Erick J. Subillaga

Dissertations and Theses

There is a large subset of retinal progenitor cells that upregulate the OTX2 gene in the developing retina of the mouse. OTX2 is a homeobox transcription factor important for the development of photoreceptors and bipolar cells. If OTX2 is knocked out, photoreceptors and bipolar cells fail to differentiate. In order for OTX2 to be activated in certain retinal populations, it requires the activity of an enhancer called OTX2ECR2. Past studies demonstrated that retinal progenitor cells that had activity of OTX2ECR2 turned into horizontal cells, which require OTX2 for cell genesis and survival, and photoreceptors which require OTX2 for cell …

Using Direct Pcr For Disaster Victim Identification Reference Samples, Mary Habib

Student Theses

Forensic genetic testing is an important tool for the identification of victims after a mass fatality event but degradation of remains, presence of PCR inhibitors, and limited amounts of sample can make testing difficult. Standard protocols typically include extraction of genetic material from recovered post-mortem samples, and from ante-mortem reference samples or families of a missing person. This is a time-consuming and laborious process and may result in the loss of trace amounts of DNA available for amplification. Incorporating workflows that bypass the extraction step and directly amplify recovered DNA for short tandem repeat (STR) profile generation has the potential …

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at …

The Central Dogma: Gene Expression, Ayisha Sookdeo

Open Educational Resources

In this lesson plan, students will learn the basic structure and function of DNA and RNA. They will also learn the process of gene expression. Finally, students will learn about the scientific contributor, Ernest Everest Just, and his contributions to the field of Biology.

Evaluating A Test For Shedding Propensity Using Tape Lifts From Different Skin Locations, Xiao M. Chen

Student Theses

The shedding propensity of a person can assist data interpretation in casework when assessing the possibility of passive transfer for DNA analysis. Past studies on shedding propensity evaluated palmar skin (washed and unwashed) deposits. This study compared different skin locations with respect to shedding propensity, and explored the potential of tape-lifts as a skin surface collection method. Eight different skin types and samples were collected with adhesive tape disks from 28 participants over three non-consecutive days; the washed and unwashed fingers from both hands, toe, and arm, neck below ear, and nape. Samples were extracted, quantified, amplified, genotyped, and evaluated …

Regulatory Non-Coding Rnas Modulate Transcriptional Activation During B Cell Development, Mary Attaway, Tzippora Chwat-Edelstein, Bao Q. Vuong

Publications and Research

B cells play a significant role in the adaptive immune response by secreting immunoglobulins that can recognize and neutralize foreign antigens. They develop from hematopoietic stem cells, which also give rise to other types of blood cells, such as monocytes, neutrophils, and T cells, wherein specific transcriptional programs define the commitment and subsequent development of these different cell lineages. A number of transcription factors, such as PU.1, E2A, Pax5, and FOXO1, drive B cell development. Mounting evidence demonstrates that non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), modulate the expression of these transcription factors directly by binding …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen

Publications and Research

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity …

Microbial-Host Dynamics And The Evolution Of Nearshore Diversity In Hippocampus Abdominalis, Jimiane L. Ashe

Dissertations, Theses, and Capstone Projects

Local adaptation is a fundamental concept at the core of evolutionary process. Devising means to break down larger concepts and systematically test internal mechanisms are key to understanding the driving forces behind the influence of environmental differences on biological systems. To understand dynamic processes in the natural world, we must strip away layers and confounding variables that may mask the signal we hope to understand. In this case seahorse species, Hippocampus abdominalis, or the pot-bellied seahorse, made an unlikely but ideal study system. The first layer to strip away was neutral genetic variation within the population. A multilocus genetic …

Molecular Mechanisms Underlying Cell Fate Choice Within Specific Retinal Lineages, Estie Schick

Dissertations, Theses, and Capstone Projects

During development, retinal progenitor cells (RPCs) divide to form all of the cell types that make up the retina. Multipotent RPCs are competent to generate all retinal cell types, while restricted RPCs form specific lineages of cells. In particular, one genetically-defined RPC type preferentially gives rise to cone photoreceptors and horizontal cells. Many of the mechanisms that are responsible for directing cell fate choice within this lineage are unknown. This thesis largely focuses on examining the development of specific cell types and subtypes from restricted RPCs and on investigating the gene regulatory events that underlie cone photoreceptor and horizontal cell …

Determination Of Human Shedding Propensity Based On Str Results, Genevieve Trapani

Student Theses

Trace DNA evidence may be discovered at a crime scene after having been deposited by a person of interest via active or passive transfer. Based on previous studies, passive transfer of one’s DNA is influenced by their shedding propensity, or probability of depositing a detectable amount of DNA through touch. Determining the shedding propensity of a person of interest can aid in trace DNA interpretation in forensic casework. This study explored STR profile quality and the presence of a DNA mixture for different skin surface locations, including fingertips before and after handwashing. As expected, unwashed fingers showed a higher prevalence …

Nmr Solution Structures Of Runella Slithyformis Rna 2'-Phosphotransferase Tpt1 Provide Insights Into Nad+ Binding And Specificity, Sébastien Alphonse, Ankan Banerjee, Swathi Dantuluri, Stewart Shuman, Ranajeet Ghose

Publications and Research

Tpt1, an essential component of the fungal and plant tRNA splicing machinery, catalyzes transfer of an internal RNA 2′-PO₄ to NAD⁺ yielding RNA 2′-OH and ADP-ribose-1′,2′-cyclic phosphate products. Here, we report NMR structures of the Tpt1 ortholog from the bacterium Runella slithyformis (RslTpt1), as apoenzyme and bound to NAD⁺. RslTpt1 consists of N- and C-terminal lobes with substantial inter-lobe dynamics in the free and NAD⁺-bound states. ITC measurements of RslTpt1 binding to NAD⁺ (K_D ∼31 μM), ADP-ribose (∼96 μM) and ADP (∼123 μM) indicate that substrate affinity is determined primarily by …

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha

Publications and Research

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). …

Not Withering On The Evolutionary Vine: Systematic Revision Of The Brown Vine Snake (Reptilia: Squamata: Oxybelis) From Its Northern Distribution, Robert C. Jadin, Christopher Blair, Sarah A. Orlofske, Michael J. Jowers, Gilson A. Rivas, Laurie J. Vitt, Julie M. Ray, Eric N. Smith, John C. Murphy

Publications and Research

The genus Oxybelis currently is composed of four taxa despite numerous studies suggesting and describing multiple taxa within the O. aeneus complex. Here, we utilize a multilocus molecular dataset (i.e. cyt b, ND4, 12S, 16S, cmos, PRLR, 3663 bp) to conduct phylogenetic analyses to assess the evolutionary history of Oxybelis. Our molecular analyses find three major lineages of Oxybelis (i.e. O. aeneus complex, O. brevirostris, O. fulgidus complex) with a sister relationship between O. brevirostris and the O. aeneus complex to the exclusion of the O. fulgidus complex. More specifically, O. aeneus appears to harbor at least …

Regulation Of A Messenger: Raising Oskar, It Takes A Village, Livia V. Bayer

Dissertations, Theses, and Capstone Projects

D. melanogaster oogenesis serves as an excellent system to study the life of an mRNA. Tremendous work has been done to understand the numerous complex mechanisms of mRNA regulation, still there is still so much that is yet to be discovered. In this thesis, I present studies I carried out to address several aspects of oskar mRNA post-transcriptional regulation. Leading me to extend our current understanding of the carefully controlled regulation of oskar mRNA life cycle via a myriad of proteins. I found that a specific NPC component, Nup154 is necessary not only for its export from the nucleus, but …

Employing High Probability Gene Choice Elements To Understand Singular Odorant Receptor Expression, Raena Mina

Dissertations, Theses, and Capstone Projects

The ability to detect odorous chemicals in the environment is the oldest of the senses necessary for survival, from escaping danger, finding mates, to locating food. It is said that humans can identify and discriminate up to a trillion different odor mixtures. For chemoreception to have such a high discriminatory power, would require a diverse population of cells dedicated for odor detection. These detector cells are the olfactory sensory neurons (OSNs), which express odorant receptors (ORs) that bind to chemical odors in the environment. In order to increase specificity and sensitivity, an essential property in olfaction is for each OSN …

Discrimination Of Monozygotic Twins Using Dna Methylation Levels Of One Cpg Site At Chromosome 3, Dino O. Robinson

Student Theses

Conventional STR typing, commonly used in forensics for human identification, poses a problem in criminal cases and paternity disputes involving monozygotic (MZ) twins because they share identical DNA sequences. To date, no routine method is available in forensics to differentiate between individuals of MZ pairs. Recently, epigenetic methods measuring differential DNA methylation patterns have been applied to MZ twin differentiation. In this study, we investigated the potential to identify MZ twins using a previously identified DNA methylation site in chromosome 3, cg18562578, in a sample of 129 MZ and 37 dizygotic (DZ) twin pairs. We used bisulfite converted saliva DNA …

Tamalin/Gras-1 Connects Glutamate Receptor Activity To The Insulin/Igf Signaling Cascade To Regulate Neuroprotection In A Nematode Model Of Excitotoxicity, Ayesha Chowdhury

Dissertations, Theses, and Capstone Projects

Brain ischemia is a major cause of debilitation and death in the United States. Excitotoxicity, a condition that arises from the accumulation of glutamate (Glu) in the synapse that leads to overactivation of Glu receptors (GluRs), is the major mechanism of neuronal damage in brain ischemia / stroke. Although it is commonly acknowledged that over activation of GluRs leads to neurodegeneration, it has been recently shown that even during excitotoxicity Glu has a concurrent important role in regulating neuroprotection. GluR-activated transcription factors seem to mediate this neuroprotection, but it remains unclear which signaling cascades and transcription factors are regulated by …

A Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Neural Development In Mice, Hao Wu, Jing Zhou, Tianhui Zhu, Ivan Cohen, Jason Dictenberg

Publications and Research

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse …

Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago

Dissertations, Theses, and Capstone Projects

A variety of biological functions depend on actin organization. The organization of actin is tightly regulated by a plethora of extracellular and intracellular signaling, scaffolding, and actin-binding proteins. Dysfunctions in this regulation lead to immune diseases, increased susceptibility to pathogens, neurodegenerative diseases, developmental disorders, and cancer metastasis. A variety of actin-dependent processes, including cell motility, are regulated by several proteins of interest: Paxillin, a scaffolding protein; WASP, an actin nucleating protein; SCAR/WAVE, another WASP family actin nucleating protein; Talin, a cortex-to-membrane binding protein; Myosin II, an F-actin contracting motor protein; and Protein Kinase C, a protein kinase. D. discoideum cells …

Receptor-Mediated Maturation Of Olfactory Sensory Neurons: A Time Course Evaluation Of Neuronal Maturation In Neomorphic Mutants, Elizabeth Miller

Theses and Dissertations

How expression of odorant receptors affects the maturation of olfactory sensory neurons (OSNs) is not known. In a time course experiment, we show that wild type OSNs mature significantly more than those expressing Neomorphic mutant receptors. We conclude that functional receptors are critical to the differentiation and survival of OSNs.

The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy

Dissertations, Theses, and Capstone Projects

Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

Phylogenetic History Of The Amy Gene Cluster In Catarrhines, Christian M. Gagnon

Theses and Dissertations

This study phylogenetically analyzed 30 AMY-related genes from 11 primates. The results show the gradual expansion of the AMY gene family which could have allowed primates to adapt to various ecological landscapes and maximize energy intake from starch-rich foods in periods of food scarcity.

Multi-Locus Phylogenetic Inference Of The Howler Monkey (Alouatta) Radiation In South America., Esmeralda Ferreira

Dissertations and Theses

Abstract

Howler monkeys (Alouatta) are the most widely distributed New World primates, ranging from southern Mexico to northern Argentina. They occur in tropical rain forests, flooded and gallery forests, and deciduous and semi-deciduous environments. Despite their importance as seed dispersers, howlers have also been known to be ecological indicators. Available phylogenetic hypotheses for this genus have used chromosomal characters, morphological characteristics, and a limited number of molecular markers and specimens. In spite of these analyses, branching patterns among howler species lineages conflict between studies or remain unresolved. Using 14 unlinked non-coding intergenic nuclear regions under both a concatenated …

The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall

Publications and Research

The Bermuda fireworm Odontosyllis enopla exhibits an extremely tight circalunar circadian behavior that results in an impressive bioluminescent mating swarm, thought to be due to a conventional luciferase-mediated oxidation of a light-emitting luciferin. In addition, the four eyes become hypertrophied and heavily pigmented, and the nephridial system is modified to store and release gametes and associated secretions. In an effort to elucidate transcripts related to bioluminescence, circadian or circalunar periodicity, as well as epitoky-related changes of the eyes and nephridial system, we examined the transcriptomic profile of three female O. enopladuring a bioluminescent swarm in Ferry Reach, Bermuda. …

Dual Graph Partitioning Highlights A Small Group Of Pseudoknot-Containing Rna Submotifs, Swati Jain, Cigdem S. Bayrak, Louis Petingi, Tamar Schlick

Publications and Research

RNA molecules are composed of modular architectural units that define their unique structural and functional properties. Characterization of these building blocks can help interpret RNA structure/function relationships. We present an RNA secondary structure motif and submotif library using dual graph representation and partitioning. Dual graphs represent RNA helices as vertices and loops as edges. Unlike tree graphs, dual graphs can represent RNA pseudoknots (intertwined base pairs). For a representative set of RNA structures, we construct dual graphs from their secondary structures, and apply our partitioning algorithm to identify non-separable subgraphs (or blocks) without breaking pseudoknots. We report 56 subgraph blocks …

Using Molecular Markers To Trace The Population History Of Volant Organisms At Differing Temporal Scales, Noah A. Burg

Dissertations, Theses, and Capstone Projects

Using molecular markers to test phylogenetic and phylogeographic hypotheses is critical for tracking the population origin of invasive, introduced species (Chapter 2, Chapter 4) and to identify the systematic relationships of disparate lineages at both shallow and deep evolutionary time scales (Chapters 3, Chapter 4). In this thesis, Sanger Sequencing was used to generate datasets based on fresh and preserved tissue from specimens collected in the field, as well as museum tissue vouchers granted from various institutions in the US and Europe. In combining these source materials, data were generated for three focal studies: 1) In the first research section …