Matching Items (10)
Filtering by
- All Subjects: pedagogy
- All Subjects: Telomerase
- Creators: Ghirlanda, Giovanna
- Creators: Rockmaker, Jody
- Status: Published
Description
In the 1970s James Watson recognized the inability of conventional DNA replication machinery to replicate the extreme termini of chromosomes known as telomeres. This inability is due to the requirement of a building block primer and was termed the end replication problem. Telomerase is nature's answer to the end replication problem. Telomerase is a ribonucleoprotein which extends telomeres through reverse transcriptase activity by reiteratively copying a short intrinsic RNA sequence to generate 3' telomeric extensions. Telomeres protect chromosomes from erosion of coding genes during replication, as well as differentiate native chromosome ends from double stranded breaks. However, controlled erosion of telomeres functions as a naturally occurring molecular clock limiting the replicative capacity of cells. Telomerase is over activated in many cancers, while inactivation leads to multiple lifespan limiting human diseases. In order to further study the interaction between telomerase RNA (TR) and telomerase reverse transcriptase protein (TERT), vertebrate TERT fragments were screened for solubility and purity following bacterial expression. Soluble fragments of medaka TERT including the RNA binding domain (TRBD) were identified. Recombinant medaka TRBD binds specifically to telomerase RNA CR4/CR5 region. Ribonucleotide and amino acid pairs in close proximity within the medaka telomerase RNA-protein complex were identified using photo-activated cross-linking in conjunction with mass spectrometry. The identified cross-linking amino acids were mapped on known crystal structures of TERTs to reveal the RNA interaction interface of TRBD. The identification of this RNA TERT interaction interface furthers the understanding of the telomerase complex at a molecular level and could be used for the targeted interruption of the telomerase complex as a potential cancer treatment.
ContributorsBley, Christopher James (Author) / Chen, Julian (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
Telomerase ribonucleoprotein is a unique reverse transcriptase that adds telomeric DNA repeats to chromosome ends. Telomerase RNA (TER) is extremely divergent in size, sequence and has to date only been identified in vertebrate, yeast, ciliate and plant species. Herein, the identification and characterization of TERs from an evolutionarily distinct group, filamentous fungi, is presented. Based on phylogenetic analysis of 69 TER sequences and mutagenesis analysis of in vitro reconstituted Neurospora telomerase, we discovered a conserved functional core in filamentous fungal TERs sharing homologous structural features with vertebrate TERs. This core contains the template-pseudoknot and P6/P6.1 domains, essential for enzymatic activity, which retain function in trans. The in vitro reconstituted Neurospora telomerase is highly processive, synthesizing canonical TTAGGG repeats. Similar to Schizosaccharomycetes pombe, filamentous fungal TERs utilize the spliceosomal splicing machinery for 3' processing. Neurospora telomerase, while associating with the Est1 protein in vivo, does not bind homologous Ku or Sm proteins found in both budding and fission yeast telomerase holoenzyme, suggesting a unique biogenesis pathway. The development of Neurospora as a model organism to study telomeres and telomerase may shed light upon the evolution of the canonical TTAGGG telomeric repeat and telomerase processivity within fungal species.
ContributorsQi, Xiaodong (Author) / Chen, Julian (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Chaput, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
Telomerase is a specialized enzyme that adds telomeric DNA repeats to the chromosome ends to counterbalance the progressive telomere shortening over cell divisions. It has two essential core components, a catalytic telomerase reverse transcriptase protein (TERT), and a telomerase RNA (TR). TERT synthesizes telomeric DNA by reverse transcribing a short template sequence in TR. Unlike TERT, TR is extremely divergent in size, sequence and structure and has only been identified in three evolutionarily distant groups. The lack of knowledge on TR from important model organisms has been a roadblock for vigorous studies on telomerase regulation. To address this issue, a novel in vitro system combining deep-sequencing and bioinformatics search was developed to discover TR from new phylogenetic groups. The system has been validated by the successful identification of TR from echinoderm purple sea urchin Strongylocentrotus purpuratus. The sea urchin TR (spTR) is the first invertebrate TR that has been identified and can serve as a model for understanding how the vertebrate TR evolved with vertebrate-specific traits. By using phylogenetic comparative analysis, the secondary structure of spTR was determined. The spTR secondary structure reveals unique sea urchin specific structure elements as well as homologous structural features shared by TR from other organisms. This study enhanced the understanding of telomerase mechanism and the evolution of telomerase RNP. The system that was used to identity telomerase RNA can be employed for the discovery of other TR as well as the discovery of novel RNA from other RNP complex.
ContributorsLi, Yang (Author) / Chen, Julian Jl (Thesis advisor) / Yan, Hao (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
ABSTRACT études; written for violin ensemble, which include violin duets, trios, and quartets, are less numerous than solo études.; These works rarely go by the title "étude;," and have not been the focus of much scholarly research. Ensemble études; have much to offer students, teachers and composers, however, because they add an extra dimension to the learning, teaching, and composing processes. This document establishes the value of ensemble études; in pedagogy and explores applications of the repertoire currently available. Rather than focus on violin duets, the most common form of ensemble étude;, it mainly considers works for three and four violins without accompaniment. Concentrating on the pedagogical possibilities of studying études; in a group, this document introduces creative ways that works for violin ensemble can be used as both études; and performance pieces. The first two chapters explore the history and philosophy of the violin étude; and multiple-violin works, the practice of arranging of solo études; for multiple instruments, and the benefits of group learning and cooperative learning that distinguish ensemble étude; study from solo étude; study. The third chapter is an annotated survey of works for three and four violins without accompaniment, and serves as a pedagogical guide to some of the available repertoire. Representing a wide variety of styles, techniques and levels, it illuminates an historical association between violin ensemble works and pedagogy. The fourth chapter presents an original composition by the author, titled Variations on a Scottish Folk Song: étude; for Four Violins, with an explanation of the process and techniques used to create this ensemble étude.; This work is an example of the musical and technical integration essential to étude; study, and demonstrates various compositional traits that promote cooperative learning. Ensemble études; are valuable pedagogical tools that deserve wider exposure. It is my hope that the information and ideas about ensemble études; in this paper and the individual descriptions of the works presented will increase interest in and application of violin trios and quartets at the university level.
ContributorsLundell, Eva Rachel (Contributor) / Swartz, Jonathan (Thesis advisor) / Rockmaker, Jody (Committee member) / Buck, Nancy (Committee member) / Koonce, Frank (Committee member) / Norton, Kay (Committee member) / Arizona State University (Publisher)
Created2011
Description
Fingerboard study is an essential component of the college guitar curriculum. A Course on Guitar Fingerboard Melody and Harmony is a method to acquire and integrate fundamental music vocabulary for the guitar performer, interpreter, improvisor, and composer, the end goal being mastery of musical vocabulary to enable artistic freedom and creative depth. This class design facilitates a solid foundation of fundamental components and provides a framework for further study and integration. It offers a concise yet intense course that consolidates, codifies, explores, and applies scale, interval, and chord vocabulary through interpretive, compositional, and improvisational engagement. This project aspires to contribute to the discipline of guitar, its canon, and its pedagogy. This programmed curriculum offers a comprehensive one-year, two-semester, college-level course on fundamental music vocabulary on the guitar fretboard. Its design facilitates a solid foundation for fundamental musical components, equips the student with a working scale and chord vocabulary, reveals how vocabulary is generated on any fretted instrument, and provides a framework for further study and integration. Semester one facilitates in-depth scale and interval study, while semester two investigates triads and seventh chords, reflecting one, two, three, and four voices textures. Each unit contains lessons, assignments, and integration activities. This document provides both teacher edition, units one through four, and student workbook, units five through eight.
Students of A Course on Guitar Fingerboard Melody and Harmony can expect dramatic strides in their understanding of musical vocabulary, its applications, and their abilities to associate and engage in real-time interpretative, compositional, and improvisational contexts. Fingerboard knowledge greatly enhances sight reading skills and enables the interpreter to find fingerings that express the rhythmic, melodic, and harmonic character of any particular musical gesture, and consequently, an entire composition. Guitar composers will be most effective when they know the possibilities and parameters of musical vocabulary on the instrument. Often, the study of vocabulary can inform and expand a composer's sonic palette and conception. For improvisers, fingerboard comprehension allows access to any interval, scale, arpeggio, or voicing the ear desires, regardless of where they happen to find themselves on the instrument in that unique moment.
ContributorsZweig, Phillip (Author) / Kim, Ji Leon (Thesis advisor) / Swartz, Jonathan (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2022
A Pedagogical Study of Selected Piano Compositions by the "Godfather of Piano Education", Zhaoyi Dan
Description
The purpose of this project is to research the pedagogical, philosophical and compositional ideals of the renowned Chinese pedagogue Zhaoyi Dan and to provide performance and pedagogical suggestions for selected piano works. Zhaoyi Dan (b. 1940) is one of the leading piano educators of the twentieth and twenty-first centuries in China. Over his sixty years of teaching, he has been given the nickname “Godfather of piano education”. He has taught many renowned concert pianists, including Yundi Li, Sa Chen, and Haochen Zhang. Twenty-nine of Dan’s students have collectively won sixty-three prizes at major international competitions. This paper will detail Zhaoyi Dan’s comprehensive teaching philosophy and methods by studying his published academic theses, piano compositions, and online master classes and seminars. The selected piano works composed by Zhaoyi Dan are presented with an introduction of each piece, brief musical description, and pedagogical suggestions. Through the study of Zhaoyi Dan’s pedagogical philosophies and selected piano works, I hope this paper will show his helpful teaching methods and add to the pedagogical piano repertoire for teachers and students.
ContributorsGuan, Ning (Author) / Creviston, Hannah (Thesis advisor) / Hamilton, Robert (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2024
Description
Telomerase is a unique reverse transcriptase that has evolved specifically to extend the single stranded DNA at the 3' ends of chromosomes. To achieve this, telomerase uses a small section of its integral RNA subunit (TR) to reiteratively copy a short, canonically 6-nt, sequence repeatedly in a processive manner using a complex and currently poorly understood mechanism of template translocation to stop nucleotide addition, regenerate its template, and then synthesize a new repeat. In this study, several novel interactions between the telomerase protein and RNA components along with the DNA substrate are identified and characterized which come together to allow active telomerase repeat addition. First, this study shows that the sequence of the RNA/DNA duplex holds a unique, single nucleotide signal which pauses DNA synthesis at the end of the canonical template sequence. Further characterization of this sequence dependent pause signal reveals that the template sequence alone can produce telomerase products with the characteristic 6-nt pattern, but also works cooperatively with another RNA structural element for proper template boundary definition. Finally, mutational analysis is used on several regions of the protein and RNA components of telomerase to identify crucial determinates of telomerase assembly and processive repeat synthesis. Together, these results shed new light on how telomerase coordinates its complex catalytic cycle.
ContributorsBrown, Andrew F (Author) / Chen, Julian J. L. (Thesis advisor) / Jones, Anne (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
Description
This research will explore the compositional approaches of Henry Cowell and John Cage to reveal piano techniques for the practice and performance of selected works. The discussion will focus on Henry Cowell’s Three Irish Legends and Six Ings, as well as John Cage’s The Perilous Night. An important contribution of Cowell was to further the use of tone clusters, applied in his Three Irish Legends by playing directly with the forearm, fists, and palm. Cowell’s Six Ings employ rhythmic experimentation, particularly in the first, second, and sixth pieces. He also uses tone color to portray specific programmatic features. John Cage greatly advanced the prepared piano from its earliest beginnings, as evidenced significantly in The Perilous Night. The present study will include advice on piano preparation, along with performance challenges and solutions.
ContributorsLiu, Xuan (Author) / Hamilton, Robert (Thesis advisor) / Campbell, Andrew (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2020
Description
The highly specialized telomerase ribonucleoprotein enzyme is composed minimally of telomerase reverse transcriptase (TERT) and telomerase RNA (TR) for catalytic activity. Telomerase is an RNA-dependent DNA polymerase that syntheizes DNA repeats at chromosome ends to maintain genome stability. While TERT is highly conserved among various groups of species, the TR subunit exhibits remarkable divergence in primary sequence, length, secondary structure and biogenesis, making TR identification extremely challenging even among closely related groups of organisms.
A unique computational approach combined with in vitro telomerase activity reconstitution studies was used to identify 83 novel TRs from 10 animal kingdom phyla spanning 18 diverse classes from the most basal sponges to the late evolving vertebrates. This revealed that three structural domains, pseudoknot, a distal stem-loop moiety and box H/ACA, are conserved within TRs from basal groups to vertebrates, while group-specific elements emerge or disappear during animal TR evolution along different lineages.
Next the corn-smut fungus Ustilago maydis TR was identified using an RNA-immunoprecipitation and next-generation sequencing approach followed by computational identification of TRs from 19 additional class Ustilaginomycetes fungi, leveraging conserved gene synteny among TR genes. Phylogenetic comparative analysis, in vitro telomerase activity and TR mutagenesis studies reveal a secondary structure of TRs from higher fungi, which is also conserved with vertebrates and filamentous fungi, providing a crucial link in TR evolution within the opisthokonta super-kingdom.
Lastly, work by collabarotors from Texas A&M university and others identified the first bona fide TR from the model plant Arabidopsis thaliana. Computational analysis was performed to identify 85 novel AtTR orthologs from three major plant clades: angiosperms, gymnosperms and lycophytes, which facilitated phylogenetic comparative analysis to infer the first plant TR secondary structural model. This model was confirmed using site-specific mutagenesis and telomerase activity assays of in vitro reconstituted enzyme. The structures of plant TRs are conserved across land plants providing an evolutionary bridge that unites the disparate structures of previously characterized TRs from ciliates and vertebrates.
A unique computational approach combined with in vitro telomerase activity reconstitution studies was used to identify 83 novel TRs from 10 animal kingdom phyla spanning 18 diverse classes from the most basal sponges to the late evolving vertebrates. This revealed that three structural domains, pseudoknot, a distal stem-loop moiety and box H/ACA, are conserved within TRs from basal groups to vertebrates, while group-specific elements emerge or disappear during animal TR evolution along different lineages.
Next the corn-smut fungus Ustilago maydis TR was identified using an RNA-immunoprecipitation and next-generation sequencing approach followed by computational identification of TRs from 19 additional class Ustilaginomycetes fungi, leveraging conserved gene synteny among TR genes. Phylogenetic comparative analysis, in vitro telomerase activity and TR mutagenesis studies reveal a secondary structure of TRs from higher fungi, which is also conserved with vertebrates and filamentous fungi, providing a crucial link in TR evolution within the opisthokonta super-kingdom.
Lastly, work by collabarotors from Texas A&M university and others identified the first bona fide TR from the model plant Arabidopsis thaliana. Computational analysis was performed to identify 85 novel AtTR orthologs from three major plant clades: angiosperms, gymnosperms and lycophytes, which facilitated phylogenetic comparative analysis to infer the first plant TR secondary structural model. This model was confirmed using site-specific mutagenesis and telomerase activity assays of in vitro reconstituted enzyme. The structures of plant TRs are conserved across land plants providing an evolutionary bridge that unites the disparate structures of previously characterized TRs from ciliates and vertebrates.
ContributorsLogeswaran, Dhenugen (Author) / Chen, Julian J-L (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Borges, Chad R (Committee member) / Arizona State University (Publisher)
Created2019
Description
The modern day tubist has an expanded collection of solo tuba repertoire that continues to grow in quantity and in difficulty, making it necessary to utilize all the tools available to improve musicianship and performance ability. In this capacity, the use of transcribed material serves as a vital method of cross training in order to develop skills which assist the performance of modern tuba literature. Rather than focusing on transcriptions solely to engage with musical eras that the tuba would not otherwise have access to, the tubist can use transcribed material as supplementary or even prerequisite repertoire.
This project examines a cross training style of studying transcriptions for the advancing tubist. Similar to how athletes cross train in two or more sports to improve their abilities, the tubist may cross train with transcriptions in order to improve the technical and musical skills required in modern tuba literature. Transcribed materials will be used to develop facility in the areas of technique, phrasing, and stylistic interpretation using three unique pieces of standard solo tuba repertoire; Krzysztof Penderecki’s Capriccio, the John Williams Tuba Concerto, and Anthony Plog’s Three Miniatures.
This project examines a cross training style of studying transcriptions for the advancing tubist. Similar to how athletes cross train in two or more sports to improve their abilities, the tubist may cross train with transcriptions in order to improve the technical and musical skills required in modern tuba literature. Transcribed materials will be used to develop facility in the areas of technique, phrasing, and stylistic interpretation using three unique pieces of standard solo tuba repertoire; Krzysztof Penderecki’s Capriccio, the John Williams Tuba Concerto, and Anthony Plog’s Three Miniatures.
ContributorsNetzer, Travis (Author) / Swoboda, Deanna (Thesis advisor) / Ericson, John (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2016