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Sequence And Target Specificity Of The C. Elegans Cell Fate Specification Factor Pos-1: A Dissertation, Brian M. Farley Aug 2012

Sequence And Target Specificity Of The C. Elegans Cell Fate Specification Factor Pos-1: A Dissertation, Brian M. Farley

GSBS Dissertations and Theses

In most metazoans, early embryogenesis is controlled by the translational regulation of maternally supplied mRNA. Sequence-specific RNA-binding proteins play an important role in regulating early embryogenesis, yet their specificities and regulatory targets are largely unknown. To understand how these RNA-binding proteins select their targets, my research focused on the C. elegans CCCH-type tandem zinc finger protein POS-1. Embryos lacking maternally supplied POS-1 die prior to gastrulation, and exhibit defects in the specification of pharyngeal, intestinal, and germline precursor cells. To identify the regulatory targets that contribute to the POS-1 mutant phenotype, we set out to determine the sequence specificity of ...


Tyraminergic G Protein-Coupled Receptors Modulate Locomotion And Navigational Behavior In C. Elegans: A Dissertation, Jamie L. Donnelly Aug 2011

Tyraminergic G Protein-Coupled Receptors Modulate Locomotion And Navigational Behavior In C. Elegans: A Dissertation, Jamie L. Donnelly

GSBS Dissertations and Theses

An animal’s ability to navigate through its natural environment is critical to its survival. Navigation can be slow and methodical such as an annual migration, or purely reactive such as an escape response. How sensory input is translated into a fast behavioral output to execute goal oriented locomotion remains elusive. In this dissertation, I aimed to investigate escape response behavior in the nematode C. elegans. It has been shown that the biogenic amine tyramine is essential for the escape response. A tyramine-gated chloride channel, LGC-55, has been revealed to modulate suppression of head oscillations and reversal behavior in response ...


Chromosome-Biased Binding And Function Of C. Elegans Drm Complex, And Its Role In Germline Sex-Silencing: A Dissertation, Tomoko M. Tabuchi Jul 2011

Chromosome-Biased Binding And Function Of C. Elegans Drm Complex, And Its Role In Germline Sex-Silencing: A Dissertation, Tomoko M. Tabuchi

GSBS Dissertations and Theses

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in the cell cycle and cancer. Recent work has unveiled a new aspect of DRM function in regulating genes involved in development and differentiation. These studies, however, were performed with cultured cells and a genome-wide study involving intact organisms undergoing active proliferation and differentiation was lacking. Our goal was to extend the knowledge of the role of DRM in gene regulation through development and in multiple tissues. To accomplish this, we employed genomic approaches to determine genome-wide targets of DRM using ...


Converging Pathways In The Regulation Of Longevity And Metabolism In Caenorhabditis Elegans: A Dissertation, Sri Devi Narasimhan Nov 2010

Converging Pathways In The Regulation Of Longevity And Metabolism In Caenorhabditis Elegans: A Dissertation, Sri Devi Narasimhan

GSBS Dissertations and Theses

The lifespan of an organism is determined by a complex array of genetic, environmental and nutritional factors. Yet single gene manipulations have been shown to significantly extend lifespan in several model organisms. Of all the genes that have been studied thus far, components of the insulin/IGF-1 signaling (IIS) pathway have emerged as the most robust regulators of longevity. In addition, IIS also regulates development, energy metabolism and the response to stress in a conserved manner. In Caenorhabditis elegans, signaling through this pathway is initiated by activation of the insulin/IGF-1 receptor tyrosine kinase DAF-2, which then activates a PI3-kinase ...


C. Elegans Metabolic Gene Regulatory Networks: A Dissertation, H. Efsun Arda Jul 2010

C. Elegans Metabolic Gene Regulatory Networks: A Dissertation, H. Efsun Arda

GSBS Dissertations and Theses

In multicellular organisms, determining when and where genes will be expressed is critical for their development and physiology. Transcription factors (TFs) are major specifiers of differential gene expression. By establishing physical contacts with the regulatory elements of their target genes, TFs often determine whether the target genes will be expressed or not. These physical and/or regulatory TF-DNA interactions can be modeled into gene regulatory networks (GRNs), which provide a systems-level view of differential gene expression. Thus far, much of the GRN delineation efforts focused on metazoan development, whereas the organization of GRNs that pertain to systems physiology remains mostly ...


Roles Of Cellular Rna-Dependent Rna Polymerases In Endogenous Small Rna Pathways In Caenorhabditis Elegans: A Dissertation, Jessica J. Vasale Jun 2010

Roles Of Cellular Rna-Dependent Rna Polymerases In Endogenous Small Rna Pathways In Caenorhabditis Elegans: A Dissertation, Jessica J. Vasale

GSBS Dissertations and Theses

The RNA interference (RNAi) pathway in Caenorhabditis elegans is a two-step, small RNA-mediated silencing pathway. Unlike in other organisms, Dicer processing of double-stranded RNA into small interfering (si) RNAs is not sufficient in worms to induce gene silencing. The activity of cellular RNA-dependent RNA polymerase (RdRP) is necessary to synthesize a secondary pool of siRNAs, which interact with a unique class of Argonaute proteins to form the functional effector complexes that mediate silencing. The aims of this thesis were to: 1) characterize the role of RdRP family members in endogenous small RNA biogenesis; 2) identify the Argonaute proteins that interact ...


Rna Recognition By The Caenorhabditis Elegans Embryonic Determinants Mex-5 And Mex-3: A Dissertation, John M. Pagano Jr. Jun 2010

Rna Recognition By The Caenorhabditis Elegans Embryonic Determinants Mex-5 And Mex-3: A Dissertation, John M. Pagano Jr.

GSBS Dissertations and Theses

Post-transcriptional regulation of gene expression is a mechanism that governs developmental and cellular events in metazoans. In early embryogenesis, transcriptionally quiescent cells depend upon maternally supplied factors such as RNA binding proteins and RNA that control key decisions. Morphogen gradients form and in turn pattern the early embryo generating different cell types and spatial order. In the nematode Caenorhabditis elegans, the early embryo relies upon several RNA binding proteins that control mRNA stability, translation efficiency, and/or mRNA localization of cell fate determinants essential for proper development.

MEX-5 and MEX-3 are two conserved RNA-binding proteins required to pattern the anterior ...


Worming To Complete The Insulin/Igf-1 Signaling Cascade: A Dissertation, Srivatsan Padmanabhan Apr 2009

Worming To Complete The Insulin/Igf-1 Signaling Cascade: A Dissertation, Srivatsan Padmanabhan

GSBS Dissertations and Theses

The insulin/IGF-1 signaling (IIS) was initially identified in C. elegansto control a developmental phenotype called dauer. Subsequently, it was realized that lifespan was extended by mutations in this pathway and became an intense focus of study. The IIS pathway regulates growth, metabolism and longevity across phylogeny and plays important roles in human disease such as cancer and diabetes. Given the large number of cellular processes that this pathway controls, understanding the regulatory mechanisms that modulate insulin/IGF-1 signaling is of paramount importance.

IIS signaling is a very well-studied kinase cascade but few phosphatases in the pathway are known ...


A Study Of Cell Polarity And Fate Specification In Early C. Elegans Embryos: A Dissertation, Soyoung Kim May 2008

A Study Of Cell Polarity And Fate Specification In Early C. Elegans Embryos: A Dissertation, Soyoung Kim

GSBS Dissertations and Theses

Asymmetric cell divisions constitute a basic foundation of animal development, providing a mechanism for placing specific cell types at defined positions in a developing organism. In a 4-cell stage embryo in Caenorhabditis elegansthe EMS cell divides asymmetrically to specify intestinal cells, which requires a polarizing signal from the neighboring P2 cell. Here we describe how the extracellular signal from P2 is transmitted from the membrane to the nucleus during asymmetric EMS cell division, and present the identification of additional components in the pathways that accomplish this signaling.

P2/EMS signaling involves multiple inputs, which impinge on the Wnt, MAPK-like ...


A Genetic Analysis Of Genomic Stability In Caenorhabditis Elegans: A Dissertation, Melissa M. Auclair Sep 2007

A Genetic Analysis Of Genomic Stability In Caenorhabditis Elegans: A Dissertation, Melissa M. Auclair

GSBS Dissertations and Theses

In humans, Bloom’s Syndrome is caused by a mutation of the RecQ helicase BLM. Patients with Bloom’s Syndrome exhibit a high amount of genomic instability which results in a high incidence of cancer. Though Bloom’s Syndrome has been intensively studied, there are still many questions about the function of BLM which need to be answered. While it is clear that loss of BLM increases genomic instability, the other effects of genomic instability on the organism aside from cancer such as a potential effect on aging, have yet to be elucidated.

In Chapter II, I identify new phenotypes ...


The Argonaute Family Of Genes In Caenorhabditis Elegans: A Dissertation, Erbay Yigit Feb 2007

The Argonaute Family Of Genes In Caenorhabditis Elegans: A Dissertation, Erbay Yigit

GSBS Dissertations and Theses

Members of the Argonaute family of proteins, which interact with small RNAs, are the key players of RNAi and other related pathways. The C. elegans genome encodes 27 members of the Argonaute family. During this thesis research, we sought to understand the functions of the members of this gene family in C. elegans. Among the Argonaute family members, rde-1 and alg-1/2have previously been shown to be essential for RNAi and development, respectively. In this work, we wanted to assign functions to the remaining members of this large family of proteins.

Here, we describe the phenotype of 31 deletion ...


Identification Of Novel (RNai DeFicient) Genes In C. Elegans: A Dissertation, Chun-Chieh G. Chen Sep 2006

Identification Of Novel (RNai DeFicient) Genes In C. Elegans: A Dissertation, Chun-Chieh G. Chen

GSBS Dissertations and Theses

RNA interference or RNAi was first discovered as an experimental approach that induces potent sequence-specific gene silencing. Remarkably, subsequent studies on dissecting the molecular mechanism of the RNAi pathway reveal that RNAi is conserved in most eukaryotes. In addition, genes and mechanisms related to RNAi are employed to elicit the regulation of endogenous gene expression that controls a variety of important biological processes. To investigate the mechanism of RNAi in the nematode C. elegans, we performed genetic screens in search of RNAi deficient mutants (rde). Here I report the summary of the genetic screens in search of rde ...


Analysis Of Polarity Signaling In Both Early Embryogenesis And Germline Development In C. Elegans: A Dissertation, Yanxia Bei Jan 2005

Analysis Of Polarity Signaling In Both Early Embryogenesis And Germline Development In C. Elegans: A Dissertation, Yanxia Bei

GSBS Dissertations and Theses

In a 4-cell C. elegans embryo the ventral blastomere EMS requires polarity signaling from its posterior sister cell, P2. This signaling event enables EMS to orient its division spindle along the anterior-posterior (A/P) axis and to specify the endoderm fate of its posterior daughter cell, E.

Wnt pathway components have been implicated in mediating P2/EMS signaling. However, no single mutants or various mutant combinations of the Wnt pathway components disrupt EMS polarity completely. Here we describe the identification of a pathway that is defined by two tyrosine kinase related proteins, SRC-1 and MES-1, which function in parallel with ...


Conserved Nucleosome Remodeling/Histone Deacetylase Complex And Germ/Soma Distinction In C. Elegans: A Dissertation, Yingdee Unhavaithaya Aug 2003

Conserved Nucleosome Remodeling/Histone Deacetylase Complex And Germ/Soma Distinction In C. Elegans: A Dissertation, Yingdee Unhavaithaya

GSBS Dissertations and Theses

A rapid cascade of regulatory events defines the differentiated fates of embryonic cells, however, once established, these differentiated fates and the underlying transcriptional programs can be remarkably stable. Here, we describe two proteins, MEP-1, a novel protein, and LET-418/Mi-2, both of which are required for the maintenance of somatic differentiation in C. elegans. MEP-1 was identified as an interactor of PIE-1, a germ-specific protein required for germ cell specification, while LET-418 is a protein homologous to Mi-2, a core component of the nuc1eosome remodeling/histone deacetylase (NuRD) complex. In animals lacking MEP-1 and LET-418, germline-specific genes become derepressed in ...