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Maintaining The Balance: Coordinating Excitation And Inhibition In A Simple Motor Circuit: A Dissertation, Hilary A. Petrash Aug 2012

Maintaining The Balance: Coordinating Excitation And Inhibition In A Simple Motor Circuit: A Dissertation, Hilary A. Petrash

GSBS Dissertations and Theses

The generation of complex behaviors often requires the coordinated activity of diverse sets of neural circuits in the brain. Activation of neuronal circuits drives behavior. Inappropriate signaling can contribute to cognitive disorders such as epilepsy, Parkinson’s, and addiction (Nordberg et al., 1992; Quik and McIntosh, 2006; Steinlein et al., 2012). The molecular mechanisms by which the activity of neural circuits is coordinated remain unclear. What are the molecules that regulate the timing of neural circuit activation and how is signaling between various neural circuits achieved? While much work has attempted to address these points, answers to these questions have ...


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 ...


A Multiparameter Network Reveals Extensive Divergence Between C. Elegans Bhlh Transcription Factors: A Dissertation, Christian A. Grove Sep 2009

A Multiparameter Network Reveals Extensive Divergence Between C. Elegans Bhlh Transcription Factors: A Dissertation, Christian A. Grove

GSBS Dissertations and Theses

It has become increasingly clear that transcription factors (TFs) play crucial roles in the development and day-to-day homeostasis that all biological systems experience. TFs target particular genes in a genome, at the appropriate place and time, to regulate their expression so as to elicit the most appropriate biological response from a cell or multicellular organism. TFs can often be grouped into families based on the presence of similar DNA binding domains, and these families are believed to have expanded and diverged throughout evolution by several rounds of gene duplication and mutation. The extent to which TFs within a family have ...


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 ...


Delineating The C. Elegans Microrna Regulatory Network: A Dissertation, Natalia Julia Martinez Apr 2009

Delineating The C. Elegans Microrna Regulatory Network: A Dissertation, Natalia Julia Martinez

GSBS Dissertations and Theses

Metazoan genomes contain thousands of protein-coding and non-coding RNA genes, most of which are differentially expressed, i.e., at different locations, at different times during development, or in response to environmental signals. Differential gene expression is achieved through complex regulatory networks that are controlled in part by two types of trans-regulators: transcription factors (TFs) and microRNAs (miRNAs). TFs bind to cis-regulatory DNA elements that are often located in or near their target genes, while microRNAs hybridize to cis-regulatory RNA elements mostly located in the 3’ untranslated region (3’UTR) of their target mRNAs.

My work in the ...


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 ...


Regulation Of Life Span By Daf-16/Forkhead Transcription Factor In Caenorhabditis Elegans: A Dissertation, Seung Wook Oh Oct 2005

Regulation Of Life Span By Daf-16/Forkhead Transcription Factor In Caenorhabditis Elegans: A Dissertation, Seung Wook Oh

GSBS Dissertations and Theses

The insulin/IGF-1 signaling pathway plays a pivotal role in life span regulation in diverse organisms. In Caenorhabditis elegans, a PI 3-kinase signaling cascade downstream of DAF-2, an ortholog of the mammalian insulin and insulin-like growth factor-1 (IGF-1) receptor, negatively regulates DAF-16/forkhead transcription factor. DAF-16 then regulates a wide variety of genes involved in longevity, stress response, metabolism and development. DAF-16 also receives signals from other pathways regulating life span and development. However, the precise mechanism by which DAF-16 directs multiple functions is poorly understood.

First, in Chapter II, we demonstrate that JNK is a novel positive regulator of ...


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 ...


Analysis Of Rna Interference In C. Elegans: A Dissertation, Alla Grishok Sep 2001

Analysis Of Rna Interference In C. Elegans: A Dissertation, Alla Grishok

GSBS Dissertations and Theses

RNA interference (RNAi) in the nematode Caenorhabditis elegans is a type of homology-dependent post-transcriptional gene silencing induced by dsRNA. This dissertation describes the genetic analysis of the RNA interference pathway and inheritance properties associated with this phenomenon. We demonstrate that the RNAi effect can be observed in the progeny of the injected animal for at least two generations. Transmission of the interference effect occurs through a dominant extragenic agent. The wild-type activities of the RNAi pathway genes rde-l and rde-4 are required for the formation of this interfering agent but are not needed for interference thereafter. In contrast, the rde-2 ...


Analysis Of Cell Polarity Signaling In C. Elegans: A Dissertation, Christian Ernest Rocheleau Dec 1999

Analysis Of Cell Polarity Signaling In C. Elegans: A Dissertation, Christian Ernest Rocheleau

GSBS Dissertations and Theses

During embryonic development of the nematode Caenorhabditis elegans, cell fates are specified by asymmetric segregation of cell fate determinants and via cell-cell signaling events. Specification of the eight-cell stage blastomere E, the endoderm progenitor cell, requires both cell signaling and asymmetric cell division. At the four-cell stage, a polarity-inducing signal from the P2 cell is required for the EMS cell to divide asymmetrically to produce an anterior daughter MS, and posterior daughter E. In the absence of signal, the EMS cell divides symmetrically to produce two daughters that adopt the MS fate. This thesis describes the identification and analyses ...