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1
Gerrits, Daphne D. "Tyrosinases of C. elegans." Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/14890.
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The cuticle of C. elegans is extensively cross-linked by covalent disulphide bridges, tyrosine bonds and possibly glutamyl-lysine bonds. Four genes predicted to be involved in the formation of tyrosine bonds have been identified in C. elegans. tyr-1 and tyr-2 map to chromosome III, tyr-3 and tyr-4 map to chromosome I. These encode tyrosinase-like enzymes. The tyrosinase genes are very similar in structure: all genes have two Cu active sites (CuA and CuB), predicted secretory leader peptides and sxc domains (found in other proteins from C. elegans and Toxocara canis). tyr-1 has an additional polyglutamine region which may be involved in protein-protein interactions. A set of cDNAs prepared from a synchronous population of worms, harvested at two hour intervals through the lifecycle, starting shortly after hatching, was used in semi-quantitative fluorescent PCR. Steady state levels of tyr-1, -2 and -4 genes are upregulated at each moult, suggesting their involvement in the synthesis of the new cuticle. tyr-3 transcripts could not be detected in this set of cDNAs, however it was isolated from a population of worms enriched in males. Studies using lacZ- and GFP-reporter genes driven by promoter fragments of the tyrosinase genes showed that tyr-4 and tyr-1 are expressed in specific subsets of hypodermal cells. In addition tyr-1 is expressed in the vulval cells. tyr-2 was found to be expressed only faintly in hypodermal cells, and showed strong expression in the uterine cells. No expression of tyr-3 was observed. These data imply that tyrosinases are not only involved of cross-linking of cuticular proteins, but are probably also involved in the generation of the egg shell.
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Schumacher, Björn. "The C. elegans p53 pathway." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-19806.
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Gustafson, Megan Alyse. "Serotonin signaling in C. elegans." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/40957.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007.Includes bibliographical references.
Wild-type animals that have been acutely food deprived slow their locomotory rate upon encountering bacteria more than do well-fed animals. This behavior, called the enhanced slowing response, is partly serotonin (5-HT) dependent. Animals mutant for the 5-HT reuptake transporter gene mod-5 slow even more than wild-type animals because endogenous 5-HT activity is potentiated. This behavior, called the hyperenhanced slowing response, can be suppressed by mutations in genes that encode proteins important for 5-HT signaling, like the 5-HT receptor encoded by mod-1 and the Ga subunit of a G protein encoded by goa-1. This ability to suppress indicates that these genes likely act downstream of or in parallel to one or more 5-HT synapse(s) that mediate(s) the enhanced slowing response. To find genes that play a role in 5-HT signaling, we screened for suppressors of the 5-HT hypersensitivity of mod-5. We found at least seven alleles of goa-i and at least two alleles of mod-1. This shows that our screen is able to target genes that play a role in endogenous 5-HT signaling. We identified two alleles of the FMRFamide-encoding gene fp-1, which was known to mediate paralysis in exogenous 5-HT. We showed that loss-of-function mutations in flp-1 confer an enhanced slowing response defect. We also identified an allele of abts-1, which encodes a bicarbonate transporter, and showed that it has defects in cholinergic signaling. We identified three mutants that show linkage to LG I, four to II, three to V and one to X, most of which display defects consistent with a role in 5-HT signaling.
(cont.) We used a candidate gene approach to find that deletions in ser-4, which encodes a metabotropic 5-HT receptor, confer 5-HT resistance. ser-4 acts redundantly with the ionotropic 5-HT receptor mod-1 to suppress the hyperenhanced slowing response of mod-5. Our genetic analysis suggests that ser-4 acts in a pathway with goa-1, in parallel to mod-1. We found that the enhanced slowing response defect of flp-1 is primarily due to its defect in transmitting a 5-HT signal and that flp-1 likely acts downstream of ser-4 and mod-1.
by Megan Alyse Gustafson.
Ph.D.
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Barry, Nicholas C. (Nicholas Craig). "Tools for connectomics in C. elegans." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/120687.
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Thesis: S.M., Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2018.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 43-46).
Efforts to model computation in biological neural networks require knowledge of the structure of the network, the dynamics that play across it, and a network simple enough to be tractable to our incipient analyses. The simplicity of the 302-node nervous system of the nematode C. elegans and its transparency have made it an attractive model organism in neuroscience for several decades. Indeed, Caenorhabditis elegans has long been touted as the only species for which the connectome is known, reconstructed by hand from electron micrographs. However, while the number and identity of neurons in C. elegans appears fixed across animals, the variability in the connections between them has not been sufficiently characterized by the above efforts, which examined only a handful of animals and required many years of human labor. Such a characterization, and, moreover, an ability to accurately assess shifts in these neural graphs on timescales compatible with the pace and statistical rigor of scientific research would significantly accelerate efforts to understand neural computation. This thesis lays the groundwork for the development of such a framework. The expansion microscopy tissue preparation platform provided the basis for the set of experiments described within, in which strategies for molecular annotation of C. elegans and the subsequent protocols for readout are examined.
by Nicholas C Barry.
S.M.
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Zhang, Xing. "Exploring fungal virulence using C. elegans." Thesis, Aix-Marseille, 2020. http://theses.univ-amu.fr.lama.univ-amu.fr/200924_ZHANG_406xehco6dvggp718z420kj_TH.pdf.
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Parmi les candidats figuraient plusieurs entérotoxines thermolabiles, une famille de protéines qui est élargie dans le génome de D. coniospora par rapport à d'autres champignons pathogènes. Nous nous sommes concentrés sur 3 (DcEntA-C). L'expression de DcEntA et de DcEntB, mais pas de DcEntC, rendait les vers malades et plus sensibles à l'infection. Normalement, l'infection par D. coniospora provoque l'induction de l'expression de gènes codant des peptides antimicrobiens des familles nlp et cnc. Il est intéressant de noter que l'expression de la seule entérotoxine DcEntA a bloqué la transcription des gènes nlp et cnc. DcEntA a agi en inhibant la translocation nucléaire du facteur de transcription STAT STA-2, nécessaire à l'expression des gènes de défense. Nous avons démontré que cet effet était spécifique car DcEntA a induit une forte expression d'un gène inductible par une infection indépendante de STA-2. En revanche, les vers exprimant l'entérotoxine DcEntB présentaient une élévation de l'expression de nlp-29 dépendante de STA-2. DcEntB est localisé au niveau du nucléole et affecte la taille et la morphologie du nucléole. La base moléculaire de ces différences et l'importance relative de ces facteurs au cours de l'infection ont été étudiées en détail. Notre résultat révélé la complexité des stratégies de virulence fongique. Globalement, en disséquant le mode d'action des différents facteurs de virulence, cette étude nous a permis de mieux comprendre la pathogénie fongique et la course évolutive entre l'hôte et l'agent pathogèneAmong the candidates were several heat-labile enterotoxins, a protein family that is expanded in the genome of D. coniospora compared to other pathogenic fungi. We focused on 3 (DcEntA-C). Expression of DcEntA and DcEntB, but not DcEntC made worms sick and more susceptible to infection. Normally, D. coniospora infection provokes the induction of expression of antimicrobial peptide genes of the nlp and cnc families. Interestingly, expression of the single enterotoxin DcEntA blocked the transcription of both nlp and cnc genes. DcEntA acted by inhibiting the nuclear translocation of the STAT transcriptional factor STA-2, required for defence gene expression. We demonstrated that this effect was specific as DcEntA induced high expression of a STA-2-independent infection-inducible gene. In contrast, worms expressing the enterotoxin DcEntB exhibited a STA-2 dependent elevation of nlp-29 expression. DcEntB was localized to the nucleolus and affected nucleolus size and morphology. The molecular basis of these differences and the relative importance of these factors during infection was explored in detail. Our result revealed the complexity of fungal virulence strategies. Overall, by dissecting the mode of action of different virulence factors, this study allowed us to understand better fungal pathogenesis and the evolutionary arms race between host and pathogen
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Boyle, Jordan Hylke. "C. elegans locomotion : an integrated approach." Thesis, University of Leeds, 2009. http://etheses.whiterose.ac.uk/1377/.
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he popular model organism Caenorhabditis elegans is a tiny nematode worm with a largely invariant nervous system, consisting of exactly 302 neurons with known connectivity. Moreover, the behavioural roles of many of these neurons have been uncovered using experimental techniques including targeted cell killing and genetic mutations. The result is an organism in which the locomotion subsystem is mapped at cellular resolution. Despite its small size and the apparent simplicity of the underlying nervous system, the worm is capable of a surprisingly rich repertoire of behaviours including navigation and foraging, mating, learning, and even rudimentary social behaviour. Indeed, this humble worm provides us with the first tangible possibility of understanding the complex behaviours of an organism from the genetic level, right up to the system level. The focus of this thesis on the locomotion system is motivated at least in part by the fact that most, if not all, of the worm’s behaviours are mediated by some form of locomotion. The main objective of this thesis is to help elucidate the mechanisms underlying C. elegans forward locomotion. In pursuit of this goal I apply an integrated methodology that emphasises collaboration between modellers like myself and experimentalists, ensuring that models are grounded in the biological reality and experiments are well designed and poignant. In contrast to previous models of C. elegans forward locomotion, the starting point of this investigation is the realization that the ability of the worm to locomote through a variety of different physical environments can shed light on the mechanism of neural and neuromuscular control of this behaviour. This work therefore begins with the presentation of several stand-alone studies, both theoretical and experimental, aimed at answering a number of preliminary questions. These include the development of a suitable model of the worm’s low Reynolds number physical environments; a preliminary study of the importance of body physics on the kinematics of locomotion; an electrophysiological modelling study of the worm’s body wall muscles; and an experimental investigation of the worm’s locomotion in different environments, ranging from liquid to dense gels. These results lead to a new perspective on the worm’s locomotion. Indeed, the conventional wisdom is that two kinematically distinct C. elegans locomotion behaviours – swimming in liquids and crawling on dense gel-like media – correspond to distinct locomotory gaits. By analysing the worm’s motion through these different media, we reveal a smooth modulation of the undulations from swimming to crawling, marked by a linear relationship between key locomotion metrics. These results point to a single locomotory gait, governed by the same underlying control mechanism. The core of this thesis is an integrated neuromechancial model of C. elegans forward locomotion. This model incorporates the results of the preliminary investigation of muscle, body and locomotion properties. The neural circuitry is grounded in the literature but simplified to a set of repeating units. Neuronal properties are modelled at different levels of abstraction, with a proof-of-concept continuous model that is used to ground assumptions in physiological data, and a simplified binary model that is then used to study the locomotion control in detail. A key property of the motor neurons in both these models is their bistable response, inspired by a recent publication demonstrating such properties in other motor neurons. Interestingly, the model is quite different to any that have come before, both in terms of its underlying neural dynamics and the behaviours that it addresses. The key achievement of this model is its ability to qualitatively and quantitatively account for locomotion across a range of media from water to agar, as well as in more complex (heterogeneous) environments. One particularly interesting result is the demonstration that a proprioceptive oscillatory mechanisms can account not only for the generation of the body undulation, but also the observed modulation in response to the changing physical environments. Indeed, this model lacks any form of centrally generated nervous system control. Finally, the model makes a number of important predictions about neuronal functions, synaptic functions and the proprioceptive response to different physical environments. A number of experiments and experimental designs are suggested to test these predictions. Preliminary experimental results are then presented to address each of these predictions. To date, these results all appear to validate the model and uncover new information about the locomotion system, hence demonstrating the power of the holistic, integrated methodology of this work. Specifically I address the role of the inhibitory D-class neurons and find evidence suggesting that they are part of the core circuit for forward locomotion, but that the phenotype associated with their removal only manifests strongly in less resistive (more fluid) media. Furthermore, I shed light on the relative roles of neural and muscle inhibition and suggest that it may be an absence of neural inhibition that underlies the forward locomotion defect of GABA defective worms.
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Mendenhall, Alexander R. "Genetic Mechanisms for Anoxia Survival in C. Elegans." Thesis, University of North Texas, 2008. https://digital.library.unt.edu/ark:/67531/metadc9062/.
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Oxygen deprivation can be pathological for many organisms, including humans. Consequently, there are several biologically and economically relevant negative impacts associated with oxygen deprivation. Developing an understanding of which genes can influence survival of oxygen deprivation will enable the formulation of more effective policies and practices. In this dissertation, genes that influence adult anoxia survival in the model metazoan system, C. elegans, are identified and characterized. Insulin-like signaling, gonad function and gender have been shown to influence longevity and stress resistance in the soil nematode, C. elegans. Thus, either of these two processes or gender may influence anoxia survival. The hypothesis that insulin-like signaling alters anoxia survival in C. elegans is tested in Aim I. The hypotheses that gonad function or gender modulates anoxia survival are tested in Aim II. Insulin-like signaling affects anoxia survival in C. elegans. Reduction of insulin-like signaling through mutation of the insulin-like receptor, DAF-2, increases anoxia survival rates in a gpd-2/3 dependent manner. The glycolytic genes gpd-2/3 are necessary for wild-type response to anoxia, and sufficient for increasing anoxia survival through overexpression. Gonad function and gender both affect anoxia survival in C. elegans. A reduction of ovulation and oocyte maturation, as measured by oocyte flux, is associated with enhanced anoxia survival in all cases examined to date. Reduction of function of several genes involved in germline development and RTK/Ras/MAPK signaling reduce ovulation and oocyte maturation while concurrently increasing anoxia survival. The act of mating does not influence anoxia survival, but altering ovulation through breeding or chemical treatment does. The male phenotype also increases anoxia survival rates independent of genotype. These studies have identified and characterized over ten different genotypes that affect adult survival of anoxia in C. elegans. Before these studies were conducted, there were no genes known to influence adult anoxia survival in C. elegans. Furthermore, these studies have begun to uncouple mechanisms of longevity and stress resistance.
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Ellis, Gregory Cody. "Regulation of polarity during C. elegans embryogenesis /." view abstract or download file of text, 2002. http://wwwlib.umi.com/cr/uoregon/fullcit?p3072580.
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Thesis (Ph. D.)--University of Oregon, 2002.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 90-98). Also available for download via the World Wide Web; free to University of Oregon users.
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Choi, Seungwon. "Regulation of Behavioral Arousal in C. elegans." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:10808.
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Animals undergo periods of behavioral quiescence and arousal in response to environmental, circadian, or developmental cues. During larval molts, C. elegans undergoes a period of profound behavioral quiescence termed lethargus. Locomotion quiescence during lethargus was abolished in mutants lacking a neuropeptide receptor (NPR-1), and was reduced in mutants lacking NPR-1 ligands (FLP-18 and -21). Wild type strains are polymorphic for the npr-1 gene, and their lethargus behavior varies correspondingly. Locomotion quiescence and arousal were mediated by decreased and increased secretion of an arousal neuropeptide (PDF-1) from central neurons. PDF receptors (PDFR-1) expressed in peripheral mechanosensory neurons enhanced touch-evoked calcium transients. Thus, a central circuit stimulates arousal from lethargus by enhancing the sensitivity of peripheral mechanosensory neurons in the body. These results define a circuit mechanism controlling a developmentally programmed form of quiescence.
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Feng, Ying. "Study of glucose transporters in C. elegans." Thesis, University of Bath, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.537773.
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The calorie restriction (CR) and insulin/IGF-I-like signalling (IIS) are two pathways regulating the lifespan of C. elegans. Recent studies showed that glucose restriction extends the lifespan of C. elegans while excessive glucose shortens the lifespan of the worms. The first step of the glucose metabolism is the transport of glucose across the plasma membrane by the glucose transporters. The work described in this thesis aims to identify glucose transporters in C. elegans and to provide a primary investigation of the in vitro and in vivo function of the identified glucose transporter. Nine putative transporters have been cloned and expressed. Out of the nice cloned putative transporters in the C. elegans genome, H17B01.1 (H17) only is identified as a fully functional glucose transporter using an oocyte expression system in which glucose transport activity is directly measured. The two transcripts of H17 are both capable of transporting glucose with high affinity, as well as transporting trehalose. Heterologous expression of H17 in mammalian CHO-T cells suggests that the protein is localised both on the plasma membrane and in the cytosol. In vitro studies of H17 show that the protein does not respond to insulin stimulation when expressed in mammalian CHO-T cell and rat primary adipocyte systems. In vivo functional studies using H17 RNAi indicate that the worm’s lifespan is not affected by the H17 knockdown. However, glucose metabolism of C. elegans (as measured by glucose oxidation to CO2 and incorporation into fat reserves) is influenced by the decreased expression of H17, especially in the daf-2 mutant strain, e1370. However, the increase of glucose metabolism caused by H17 knockdown observed in daf-2 mutant is inhibited in the age-1 and akt-1 mutant strains. The findings reported in this thesis suggest that the H17 glucose transporter may play an important role glucose metabolism in C. elegans and that this transport and metabolism is influenced by insulin receptor activity and serine kinase cascades.
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Winter, Peter B. "Quantifying Complex Behavioral Phenotypes in C. elegans." Thesis, Northwestern University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10043987.
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The study of C. elegans has led to ground-breaking discoveries in gene-function, neuronal circuits, and physiological responses. However, subtle behavioral phenotypes, are often difficult to measure and reproduce across experiments. As part of my dissertation work, I used experimental and computational techniques to quantify and model the dynamics of movement and reproductive behaviors. For movement behaviors, I developed a mathematical approach to correcting the uncertainty of tracking individual animals in a free-moving population, created behavioral profiles for each individual, and used a network to reveal the progression of behavioral changes in the aging process. For reproductive behaviors, I used perturbations in temperature to dissect the key processes that modify the dynamics of the C. elegans reproductive system. The primary goal of creating this set of tools and approaches was to acquire high-quality data for mathematically modeling how individuals respond to environmental stress and modify their behaviors during ageing.
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Kerr, Rex Alexander. "Imaging excitable cell activity in C. elegans /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2002. http://wwwlib.umi.com/cr/ucsd/fullcit?p3064472.
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Chocian, Karolina. "Chromatin regulation of lifespan in C. elegans." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:ac80efde-7588-48e8-844c-26961e86bda4.
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The biological basis of lifespan regulation is a subject of intense interest, and epigenetic control of gene expression is thought to play an important role in the ageing process. A library of RNAi clones against chromatin factors was used to screen for their effects on lifespan in C.elegans, utilising microscopic examination of lipofuscin accumulation as a primary biomarker of ageing. A secondary RNAi screen involving full lifespan monitoring confirmed knock-downs of four genes, isw-1, cbp-1, mes-2 and jmjd-3.2, results in extension of lifespan. The use of mutant alleles of these genes also resulted in statistically significant lifespan extension. Intriguingly, three of those genes encode H3K27 modifiers: cbp-1 is an acetyl transferase, whilst mes-2 and jmjd-3.2 are H3K27 methyltransferase and demethylase respectively. Mutation in another gene of the jmjd-3.2 family, utx-1, is also known to have a lifespan prolonging effects by increasing H3K27 methylation on the daf-2 promoter (Jin et al, 2012). In addition to its lifespan effects, utx-1 is also an essential developmental gene. Its role in development has, however, been confirmed to be independent of its demethylase activity (Vandamme et al. 2012) raising questions about the biological significance of UTX-1- mediated H3K27 demethylation. I used a demethylase-dead form of UTX-1 to demonstrate that enzymatic activity is absolutely required for UTX-1 function in lifespan regulation. Intriguingly, it is not just utx-1 loss of function that causes lifespan extension; overexpression of utx-1 from a transgenic array is associated with even more dramatic lifespan extension. Moreover, mes-2 and jmjd-3.2 overexpression also increases the lifespan of transgenic animals. Interestingly, however, lifespan extension driven by overexpression of jmjd-3.2 is not dependent on its demethylase function, suggesting a different mode of action to utx-1. Epistasis analysis suggests that the insulin signalling pathway is a crucial target of regulation for all the factors I identified, but ChIP analysis implies that lifespan extension driven by utx-1 overexpression may involve a different pathway from H3K27me3 regulation at the daf-2 locus. Overall, this work pinpoints H3K27 modifications at key target genes as critical determinants of longevity, and furthermore identifies the crucial importance of the fine balance of factors controlling H3K27 methylation status.
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Zhao, Beibei. "Genetic analysis of reversal behavior in C. elegans." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19627.
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Caenorhabditis elegans" locomotion consists of long forward crawling interrupted by short spontaneous reversals. We identified several intrinsic and extrinsic variables that influence the reversal frequency. In particular, reversal frequency can be transiently suppressed by touch. The genes glr-1 and nmr-1, which encode subunits of AMPA- and NMDA-type glutamate receptors, play a central role in touch-induced reversal suppression. Thus, reversal behavior is a motor output reflecting the integration of sensory inputs that display a form of memory. Food has a dramatic effect on reversal frequency that depends on chemosensation. Wild-type worms dramatically reduce reversal frequency on food but chemosensory mutants do not. A null allele of eat-2, a gene necessary for the proper response to food, confers a hyperreversal phenotype. eat-2 also enhances dauer formation in a serotonin deficient genetic background. These phenotypes do not appear to result from the effect of eat-2 on eating efficiency.
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Wong, Yan Fung. "MAB-30 functions to maintain cell identity of sensory ray in C. elegans /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202008%20WONG.
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Kim, Dae Young 1968. "Role of cki-2 during development in C. elegans." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102991.
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Rapid progress has been made toward understanding the significance of CDK inhibitor proteins (CKIs) in the regulation of cell cycle progression. The overall goal of this study has been targeted to further expand our knowledge of CKI function through the investigation of a previously uncharacterized CKI named cki-2 during development in C. elegans. The characterization of cki-2 using a reverse genetic approach called co-suppression has revealed a novel mechanism that cki-2 and its related cell cycle regulators are required for the appropriate elimination of centrioles during oogenesis. Loss of cki-2 in the germ line caused perdurance of centrioles into the one-cell embryo, resulting in supernumerary centrosomes and aberrant cell divisions in the first cell cycle. This was significantly suppressed by reduction of cyclin E and a Cdk2 homologue, indicating that these cell cycle regulators are involved in this critical developmental process. In order to further understand the function of cki-2, a yeast two-hybrid screen was conducted which allowed us to identify three CKI-2 interacting proteins: orthologues of PCNA (PCN-1), SUMO (SMO-1), and a RING finger protein called RNF-1. CKI-2 has functionally separable domains in its amino (Cyclin/Cdk binding)- and carboxy (PCNA binding)-terminus and they exert distinct roles in cell cycle progression. It was observed that CKI-2 is covalently modified by SUMO on its N-terminus and this causes CKI-2 to relocalize to thr nucleolus, which is associated with its rapid degradation. Since many RING finger proteins act as components of the multi-subunit E3 ubquitin ligases, we speculated that RNF-1 might be involved in the CKI-2 degradation. This possibility was tested by co-expression of RNF-1 with CKI-2, revealing that co-expression of RNF-1 suppresses the embryonic lethality caused by the CKI-2 overexpression and moreover, this is correlated with an increased rate of CKI-2 degradation. In addition, western blot analyses performed on different genetic backgrounds suggested that the CKI-2 degradation occurs in an ubiquitin-dependent manner through the proteasome-mediated proteolysis pathway. Furthermore, a yeast-based assay developed to test a possible role of SUMO in modulating the CKI-2/RNF-1 interaction demonstrated that SUMO may antagonize the interaction between CKI-2 and RNF-l, these highlighting an intriguing model that appropriate levels of CKI-2 are regulated through ubiquitin-dependent proteolysis mediated by RNF-l, and which maybe modulated by SUMO.
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Harrison, Neale. "Mutational analysis of α-catenin in C. elegans." Thesis, University of Aberdeen, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=56259.
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The long held view of adherens junctions being a rigid complex has recently been questioned. At the centre of this is α-catenin and the finding that it can not bind both β-catenin and actin simultaneously. Isolation of a viable α-catenin mutant in the C. elegans homologue hmp-1 provided an excellent opportunity to study this dogma for the first time in a whole organism. The work presented in this thesis aimed to characterise this mutation (hmp-1(fe4)) and isolate any potential suppressors of it. On isolation of suppressors, these were used along with hmp-1(fe4) to investigate α-catenin/hmp-1s role at adherens junctions and how this overlaps with its role in regulating the actin cytoskeleton. This study has demonstrated that a number of suppressors of hmp-1(fe4) do exist and that they are all intragenic. In addition, the suppressors are capable of complementing a hmp-1 null strain in hmp-1(fe4)s absence. Further analysis of these mutations by GFP labelling revealed that these mutations alter the proteins pattern of localisation. It is thought that this alteration in localisation is the cause for the suppressor’s suppressive effect on hmp-1(fe4). Finally the characterisation of a random C. elegans mutant that arose from the hmp-1(fe4) study but was initially not related to it was later shown to have a synthetic lethal effect when in combination with hmp-1(fe4) and therefore a role that is dependent on a fully function α-catenin/hmp-1.
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Mendenhall, Alexander R. Padilla Pamela Ann Fox. "Genetic mechanisms for anoxia survival in C. elegans." [Denton, Tex.] : University of North Texas, 2008. http://digital.library.unt.edu/permalink/meta-dc-9062.
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King, Kevin V. "Signaling components in development and life span determination in C. elegans /." free to MU campus, to others for purchase, 1998. http://wwwlib.umi.com/cr/mo/fullcit?p9901251.
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Bringmann, Henrik Philipp. "Experiments concerning the mechanism of cytokinesis in Caenorhabditis elegans embryos." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2007. http://nbn-resolving.de/urn:nbn:de:swb:14-1170257008922-66010.
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In my thesis I aimed to contribute to the understanding of the mechanism of cytokinesis in C. elegans embryos. I wanted to analyze the relative contributions of different spindle parts – microtubule asters and the midzone - to cytokinesis furrow positioning. I developed a UV laser-based severing assay that allows the spatial separation of the region midway between the asters and the spindle midzone. The spindle is severed asymmetrically between one aster and the midzone. I found that the spindle provides two consecutive signals that can each position a cytokinesis furrow: microtubule asters provide a first signal, and the spindle midzone provides a second signal. The use of mutants that do not form a midzone suggested that the aster-positioned furrow is able to divide the cell alone without a spindle midzone. Analysis of cytokinesis in hypercontracile mutants suggests that the aster-positioned cytokinesis furrow and the midzone positioned furrow inhibit each other by competing for cortical contractile elements. I then wanted to identify the molecular pathway responsible for cytokinesis furrow positioning in response to the microtubule asters. To this end, I performed an RNAi screen, which identified a role for LET-99 in cytokinesis: LET-99 appeared to be required for aster-positioned cytokinesis but not midzone-positioned cytokinesis. LET-99 localizes as a cortical band that overlaps with the cytokinesis furrow. Mechanical displacement of the spindle demonstrated that the spindle positions cortical LET-99 at the site of furrow formation. The furrow localization of LET-99 depended on G proteins, and consistent with this finding, G proteins are also required for aster-positioned cytokinesis. (Anlage: Quick time movies, 466, 67 MB)
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Lambert, Laura A. "Phenotypic characterization of PNPase knockdown in C. elegans." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3757.
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The multifunctional exoribonuclease protein PNPase is implicated as a potential target for cancer therapy as well as causing mitochondrial disorders in humans, but there has yet to be a whole animal knockdown model created. In this study, C. elegans was used to investigate the effect of knocking down pnpt-1, the gene that encodes PNPase. It was discovered that pnpt-1 knockdown significantly extends lifespan via an increase in superoxide production similar to other known mitochondrial lifespan extension pathways. Additionally, mitochondrial networks, size and respiration are affected indication of other mitochondrial dysfunction..
PNPase is also known to transport small RNAs into the mitochondria which in turn can affect mitochondria RNA splicing and translation of proteins involved in respiration. Further investigation showed a significant accumulation of polycistronic mitochondrial transcripts in knockdown animals. Lastly, this model has shown that PNPase knockdown is functionally comparable across species and is a viable model for future studies.
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Wheeler, Jeanna M. "Genetic analysis of rhythmic behavior in C. elegans /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/10246.
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Bowen, Caroline Sarah. "RNA-degradation in the nematode worm C. elegans." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487134.
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RNA turnover is necessary to ensure correct levels of gene expression, through posttranscriptional gene regulation and to remove aberrant mRNA transcripts, thereby maintaining RNA quality. Here we examine processes of RNA degradation in C. elegans, based on a functional investigation of the C. elegans components of RNA degradation pathways, focusing specifically on the exosome components, identified from sequence similarity to other organisms. RNAi and available mutants have been used to show that disruption of the exosome complex, through the targeted degradation of individual components, results in worms with severe developmental problems including slowed growth rates and developmental defects. Full length fluorescent tagged exosome components were generated, and have shown expression to be largely confined to the nuclei of all cells, including the germ line. Phenotypes associated with depletion of the exosome components are attributed to effects on rRNA processing. When exosome components are silenced, there is a failure of the degradation of specific cleaved rRNA precursors, which in tum interferes with ribosome function and subsequently protein synthesis. The investigation of the nature of these rRNA processing defects, as well as the role of the exosome in other RNA pathways such as RNAi and NMD, are presented. Finally genes involved in ribosome biogenesis are investigated, depletion of which has significant effects on development, causing. germ line tumours similar to those seen for exosome depletion.
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Philbrook, Alison M. "Molecular Mechanisms Underlying Synaptic Connectivity in C. elegans." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/966.
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Proper synaptic connectivity is critical for communication between cells and information processing in the brain. Neurons are highly interconnected, forming synapses with multiple partners, and these connections are often refined during the course of development. While decades of research have elucidated many molecular players that regulate these processes, understanding their specific roles can be difficult due to the large number of synapses and complex circuitry in the brain. In this thesis, I investigate mechanisms that establish neural circuits in the simple organism C. elegans, allowing us to address this important problem with single cell resolution in vivo.
First, I investigate remodeling of excitatory synapses during development. I show that the immunoglobulin domain protein OIG-1 alters the timing of remodeling, demonstrating that OIG-1 stabilizes synapses in early development but is less critical for the formation of mature synapses. Second, I explore how presynaptic excitatory neurons instruct inhibitory synaptic connectivity. My work shows that disruption of cholinergic neurons alters the pattern of connectivity in partnering GABAergic neurons, and defines a time window during development in which cholinergic signaling appears critical. Lastly, I define novel postsynaptic specializations in GABAergic neurons that bear striking similarity to dendritic spines, and show that presynaptic nrx-1/neurexin is required for the development of spiny synapses. In contrast, cholinergic connectivity with their other postsynaptic partners, muscle cells, does not require nrx-1/neurexin. Thus, distinct molecular signals govern connectivity with these two cell types. Altogether, my findings identify fundamental principles governing synapse development in both the developing and mature nervous system.
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Suh, Christopher D. Y. "Identification of axon guidance molecules in C. elegans /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2006. http://uclibs.org/PID/11984.
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Ibáñez, Ventoso Carolina. "Study of extracellular matrix synthesis in C. elegans." Thesis, University of Glasgow, 2003. http://theses.gla.ac.uk/5624/.
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The epithelial monolayer of cells surrounding the animal, the hypodermis, Synthesises five cuticles during the nematode life cycle. The first cuticle is formed within the egg, prior to hatching, and the remainder towards the end of each larval stage. Because of the structural role of the cuticle, mutations in genes involved in assembly of this ECM can cause a spectrum of effects from lethality late in embryogenesis to alterations in the nematode shape. The severity of phenotype correlates with the severity of cuticle synthesis defects. Accordingly, two distinct mutant alleles that cause death after embryonic elongation, possibly due to failure in synthesising an intact cuticle, were characterised . One mutant, ij15, was isolated from a forward genetic screen previously performed (I. Johnstone, Glasgow University, Glasgow, UK). ij15 defines mutationally the gene stc-1, which encodes a HSP70-like protein possibly localised in the secretory pathway. The other mutant, h402, defines mutationally the gene let-607. A second let-607 allele, h189, which results in larval lethaity at the L2 stage was also analysed in this study. let-607 corresponds to the predicted gene F57B10.1, which encodes a putative bZIP transcription factor. Both stc-1 and let-607 are expressed in the hypodermis at all developmental stages. Furthermore, disruption of the function of either stc-1 or let-607 by mutation or RNAi affects cuticle synthesis in different ways. Thus, stc-1 and let-607 encode for a HSP70-like protein and a putative bZIP transcription factor required for synthesis of the cuticular ECM in C. elegans. In addition, this study defines C. elegans mutant phenotypes that can be used as indicators for gene products with controlling roles in the synthesis of this ECM.
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Johari, Shazlina. "Microsystems for C. elegans Mechanics and Locomotion Study." Thesis, University of Canterbury. Mechanical Engineering, 2013. http://hdl.handle.net/10092/8086.
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Studying animal mechanics is crucial in order to understand how signals in the neuromuscular system contribute to an organism’s behaviour and how force-sensing organs and sensory neurons interact. In particular, the connection between the nerves and the muscles responsible for the force generation in the neuromuscular system needs to be established. Knowledge of the locomotion forces can be beneficial for the development of therapies for muscle disorders, neurodegenerative and human genetic diseases, such as muscular dystrophy. The simplicity of the nematode Caenorhabditis elegans’ (C. elegans) nervous system, which is limited to 302 neurons, has made it an excellent model organism for studying animal mechanics which include mechanosensation and locomotion at the neuronal level.
The advent of miniaturized force sensing devices has led to the proposal of various approaches for measuring C. elegans locomotion forces. However, these existing devices are relatively complex, involving complicated microfabrication procedures and are incapable of measuring forces exerted by C. elegans in motion. This thesis addresses these shortcomings by introducing a force sensor capable of continuously measuring the forces generated by C. elegans in motion. The system consists of a micropillar-based device made of polydimethylsiloxane (PDMS) only and a vision-based algorithm for resolving the worm force from the deflection of the cantilever-like pillars. The measured force is horizontal and equivalent to a point force acting at half of the pillar height. The microdevice, sub-pixel resolution for visual tracking of the deflection, and experimental technique form an integrated system for measuring dynamic forces of moving C. elegans with force resolution of 3.13 uN for worm body width of 100 um. A simple device fabrication process based on soft-lithography and a basic experimental setup, which only requires a stereo microscope with off-the-shelf digital camera mean that this method is accessible to most biological science laboratories.
The results demonstrate that the proposed device is capable of quantifying multipoint forces of moving C. elegans rather than single-point forces for a worm sample. This allows one to simultaneously collect force data from up to eight measurements points on different worm body parts. This is a significant step forward as it enables researchers to explicitly quantify the relative difference in forces exerted by the worm’s different body segments during the worms’ movements. The device’s capability to determine multipoint forces during nematode motion can also generate meaningful data to compare forces associated with different worm body muscles, gaining new understanding on how these muscles function. The forces measured during locomotion in the micropillars could also be used to differentiate mutant phenotypes. Apart from locomotion forces, the device is also capable of conducting concurrent measurement of other locomotion parameters such as speed, body amplitude and wavelength, as well as undulation frequency. This additional information can be useful to further quantify phenotypic behaviour of C. elegans and deepen the understanding of the theory behind worm locomotion forces.
The relationship between C. elegans locomotion forces and their environment has also been analyzed by variation of the pillar arrangement and spacing. The results indicate that the microstructured environment significantly affects the worm’s contraction force, locomotion speed and the undulation frequency. In addition, an alternative measurement technique was provided to measure worm forces on other substrates, such that worm locomotion behaviour in varying environments can be investigated further. The combination of the conventional measurement technique with the findings of worm locomotion on a glass substrate reported show promise for biological measurements and other sensing application such as tactile force. Additional functions of on-chip worm selection, sorting, and imaging have also been integrated with the device, rendering its potential to accommodate for high-throughput application of C. elegans force measurement and locomotion studies in the future.
The primary contributions of this thesis are centered around four topics: the development of the PDMS micropillar array and its application to study C. elegans locomotion forces, the analysis of C. elegans muscular forces and locomotion patterns in microstructured environments, the investigation of the worm locomotion forces using different substrates and finally the integration of the PDMS micropillar with PDMS microvalve for on-chip worm selection and imaging. Although the results presented in this thesis focus on wild type C. elegans, the method can be easily applied to its mutants and other organisms.
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Thompson-Peer, Katherine Louise. "Transcriptional Regulation of Synapse Remodeling in C. elegans." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10131.
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The ability of a neuron to alter its synaptic connections during development is essential to circuit assembly. Synapse remodeling or refinement has been observed in many species and many neuronal circuits, yet the mechanisms defining which neurons undergo remodeling are unclear. Moreover, the molecules that execute the process of remodeling are also obscure. To address this issue, we sought to identify targets of the transcription factor unc-55 COUP-TF, which acts as a cell-specific repressor of synapse remodeling in C. elegans. unc-55 COUP-TF is expressed in VD neurons, where it prevents synapse remodeling. DD neurons can remodel synapses because they do not express unc-55 COUP-TF. Ectopic expression of unc-55 COUP-TF in DD neurons prevents remodeling. We identified the transcription factor Hunchback-like hbl-1 as a target of UNC-55 COUP-TF repression. Differential expression of hbl-1 explains the cell-type specificity of remodeling. hbl-1 is expressed in the DD neurons that are capable of remodeling, and is not expressed in the VD neurons that do not remodel. In unc-55 mutants, hbl-1 expression increases in VD neurons where it promotes ectopic remodeling. Moreover, hbl-1 expression levels bidirectionally regulate the timing of DD remodeling, as increases in hbl-1 cause precocious remodeling while decreases in hbl-1 cause remodeling delays. Finally, hbl-1 coordinates heterochronic microRNA and neuronal activity pathways to regulate the timing of remodeling. Increases or decreases in circuit activity cause increases or decreases in hbl-1 expression, and consequently early or delayed remodeling. Thus, convergent regulation of hbl-1 expression defines a genetic mechanism that patterns activity-dependent synaptic remodeling across cell types and across developmental time. We identified other targets of UNC-55 COUP-TF regulation using gene expression profiling, and implicate some of these factors in the regulation of remodeling using functional genomic screens. Our work suggests roles for conserved networks of transcription factors in the regulation of remodeling. We propose a model in which hbl-1 and other targets of unc-55 COUP-TF transcriptional repression are responsible for regulating synapse remodeling in C. elegans.
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Zhang, Sihui. "Control of sex myoblast migration in C. elegans." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/51213.
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Cell migration is critical in generating complex animal forms during development; misregulation of migration contributes to pathological conditions such as cancer metastasis. Thanks to its easily traceable cell lineages in a transparent body and a compact genome accessible to a wealth of genetic manipulations, the use of the nematode C. elegans as a model system has greatly advanced our understanding of mechanisms governing cell migration conserved through higher organisms. Among several migration processes in C. elegans, sex myoblast (SM) migration is an attractive system that has a simple and well-defined migratory route along the ventral side from the posterior to the precise center of the gonad. A multitude of guidance mechanisms control SM migration, many of which are likely to be conserved in other migratory processes.Similar to vertebrate systems, C. elegans uses Rho family small GTPases to regulate the engine of cell motility, the actin cytoskeleton, in response to guidance cues. The differential utilizations of Rho GTPases in distinct processes in vivo remain a central question in the study of Rho GTPases. I investigated how Rho GTPases regulate different aspects of SM migration, and found that Cdc-42/CDC42 functions in the anteroposterior migration, whereas MIG-2/RhoG and CED-10/Rac1 control ventral restriction independently of FGF and SLIT/Robo signaling. The relative difficulty in perturbing SM migration using constitutively active Rho GTPases compared to other migration processes illustrates the robustness of the mechanisms that control SM migration.
On a technical aspect, I established a nematode larval cell culture system that allows access to postembryonic cells. Compared to the flourishing genetic researches in C. elegans, there are few studies of molecules that also extend to the subcellular level in postembryonic development, mainly due to the lack of a larval cell culture system. I developed a novel method combining SDS-DTT presensitization of larval cuticles and subsequent pronase E digestion. My method efficiently isolates both low- and high-abundance cell types from all larval stages. This technical advance will not only facilitate studies such as regulation of actin dynamics with high-resolution microscopy, but is beginning to be used by researchers to tackle cell-type specific questions through profiling methods as gene expression analysis.
Ph. D.
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Yao, Chen. "MODELING LRRK2-ASSOCIATED PARKINSON’S DISEASE IN C. ELEGANS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1333741130.
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Williams, Paul David Edward. "Neuromodulation in a Nociceptive Neuron in C. elegans." University of Toledo / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1515763554908573.
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Park, Ji S. "CYCLIC GMP: A SATIETY SIGNAL IN C. ELEGANS." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3851.
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Appetite control and satiety mechanisms help animals maintain energy homeostasis; however, these mechanisms can be misregulated, leading to overweight and obesity. Caenorhabditis elegans is an excellent model system to study appetite and satiety because of its conserved behavioral aspects of satiety and conserved molecular mechanisms. ASI senses nutrition and its activity is required for the behavioral state of satiety quiescence. The purpose of this thesis project was to elucidate the function of cGMP signaling in ASI by looking at behavioral effects from the pharmacological use of sildenafil (Viagra), a PDE inhibitor, and the effects on ASI activation from mutating guanylyl cyclase DAF-11. Sildenafil treatment increases satiety quiescence and decreases fat storage in a PDE-dependent manner. The daf-11 mutation decreased overall fluorescence intensity of ASI activation and the frequency at which ASI activated by about 50% compared to wild-type worms, suggesting that DAF-11 plays an important role in ASI to promote satiety.
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McLachlan, Ian Gordon. "Genetic control of dendrite morphogenesis in C. elegans." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493511.
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The shapes and attachments of cells determine the machinery of organs; for example, the shapes and attachments of neurons and glia establish the wiring of the brain. To understand how neuronal dendrites obtain their morphologies and make the appropriate connections, we used C. elegans sense organs as models. Previous work identified a requirement for the extracellular matrix protein DYF-7 in dendrite extension: DYF-7 anchors dendrites dendrite endings at the embryonic nose while neuronal cell bodies migrate away, and in its absence, dendrites fail to extend. Here, we show that these dendrites are part of a sensory epithelium composed of glial cells and neurons. The dendrites are ensheathed by glial cells, form adherens junctions onto glia, and are stabilized at their apical surfaces by the extracellular matrix protein DYF-7. In dyf-7 mutants, the pulling force of cell migration causes this sensory epithelium to rupture along the glia:glia junctions. By comparison, dendrites of the URX and BAG neurons are intimately connected to the external surface of glial cells but are not known to form adherens junctions and are not affected in dyf-7 mutants. To identify factors required for URX and BAG dendrite extension, we performed forward genetic screens for dendrite extension defects in these cells and identified mutations in the cytoplasmic protein GRDN-1/Girdin and the adhesion molecule SAX-7/L1CAM. We show that in wild-type embryos, URX and BAG dendrites also extend by attaching to the nose and then stretching during embryo elongation but, in grdn-1 embryos, they fail to remain attached. GRDN-1 can promote dendrite attachment by acting in glia—it localizes to glial endings and causes localized accumulation of SAX-7, creating an adhesive compartment where dendrites attach. Thus, GRDN-1 and SAX-7 determine dendrite length by positioning a neuron-glia attachment site that couples dendrite extension to embryonic growth. Finally, we identified several other mutants with URX dendrite morphogenesis defects, including overgrowth of the URX dendrite; some have been mapped to genes associated with the cytoskeleton. Together, these studies define genetic mechanisms that control morphogenesis of distinct classes of sensory dendrites through specific adhesive interactions with their glial neighbors.Medical Sciences
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Labrador, Gonzalez Leticia. "Roles of SPD-3 during C. elegans meiosis." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9563.
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Correct chromosome segregation during meiosis requires that the paternal and maternal copies of each chromosome, known as homologues, recognise and pair with one another before they can undergo meiotic recombination. Defects in this process lead to sterility and the formation of aneuploid gametes, which is the leading cause of birth defects in humans. In this study the process of homologue pairing during meiosis has been investigated in C. elegans, an organism especially well suited for meiotic studies. During a genetic screen for meiotic mutants, several mutants with defects in meiotic chromosome segregation were isolated. One of these mutants, me85, was identified as a new allele of the spd-3 gene, which had previously been shown to be required for mitotic divisions in the early embryo. spd-3(me85) mutants display defects in homologue pairing similar to those observed in mutants lacking SUN-1 or ZYG-12, two proteins that form a bridge across the nuclear envelope (NE). This bridge transmits cytoskeletal forces generated outside the nucleus to meiotic chromosomes inside the nucleus, thereby facilitating chromosome clustering, a process that is though to facilitate homology search. The localisation of SUN-1 and ZYG-12 to the NE is not affected in spd-3(me85) mutants and chromosomes remain tethered to the NE. However, live imaging experiments in spd-3(me85) mutants demonstrate that the movement of chromosomes through the NE is severely impaired, which results in lack of chromosome clustering. Knocking down the activity of the dynein-dynactin complex by RNAi resulted in a phenocopy of the chromosome clustering defects observed in spd-3(me85) mutants, although dynein localisation is not affected in spd-3(me85) mutants. Interestingly, the SPD-3 protein localizes outside the nucleus in the germline. These observations suggest that SPD-3 affects the earliest steps of homologue pairing by regulating the cytoskeletal forces outside the nucleus.
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Kumsta, Caroline. "The effect of oxidative stress on C. elegans." kostenfrei, 2008. http://mediatum2.ub.tum.de/doc/678556/678556.pdf.
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Johnstone, Duncan Bruce. "Genetic analysis of potassium channels in C. elegans /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/4983.
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Buchwitz, Brian. "Chromosome segregation in the holocentric organism C. elegans /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/4996.
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Arda, H. Efsun. "C. Elegans Metabolic Gene Regulatory Networks: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/479.
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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 unexplored.
My work has focused on delineating the first gene regulatory network of the nematode Caenorhabditis elegans metabolic genes, and investigating how this network relates to the energy homeostasis of the nematode. The resulting metabolic GRN consists of ~70 metabolic genes, 100 TFs and more than 500 protein–DNA interactions. It also includes novel protein-protein interactions involving the metabolic transcriptional cofactor MDT-15 and several TFs that occur in the metabolic GRN. On a global level, we found that the metabolic GRN is enriched for nuclear hormone receptors (NHRs). NHRs form a special class of TFs that can interact with diffusible biomolecules and are well-known regulators of lipid metabolism in other organisms, including humans. Interestingly, NHRs comprise the largest family of TFs in nematodes; the C. elegans genome encodes 284 NHRs, most of which are uncharacterized. In our study, we show that the C. elegans NHRs that we retrieved in the metabolic GRN organize into network modules, and that most of these NHRs function to maintain lipid homeostasis in the nematode. Network modularity has been proposed to facilitate rapid and robust changes in gene expression. Our results suggest that the C. elegans metabolic GRN may have evolved by combining NHR family expansion with the specific modular wiring of NHRs to enable the rapid adaptation of the animal to different environmental cues.
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Morbidoni, Valeria. "C. elegans as model to study neurometabolic conditions." Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3422830.
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The are several advantages in using Caenorhabditis elegans as organism model, among others its small size, the fast vital cycle and the easiness to maintain it in culture. Since between 60 and 80% of human genes have an orthologue in the worm genome, it has already been employed to investigate mitochondrial disorders, neurodegenerative diseases and also to search for neurotoxins and neuroprotective drugs.
During my PhD program I used C. elegans as a model to study genes whose function is unknown or not fully understood and potentially involved in neurometabolic diseases. At this purpose I performed RNA interference (RNAi) experiments and CRISPR/Cas9 genome editing to generate knockdown and knockout (KO)/knock-in worm models, that were then extensively phenotypically characterized.
Cytochrome c oxidase (COX) is the terminal enzymatic complex of the mitochondrial respiratory chain. Mutations in COX genes are responsible for COX deficiency, which is the most frequent cause of mitochondrial encephalomyopathies. COX16 is a COX assembly factor, with a homologue in the worm genome, that is cox-16.
By a COX specific histochemical staining we found that cox-16 is required for COX biogenesis and function, since its knockdown in nematodes causes COX deficiency. These results confirm what was previously obtained in a COX16 KO cellular model, with the advantage of having a multicellular model that could be used for drug screening, since no cure is available so far for COX deficiencies.
MYTHO is a recently identified FOXO-dependent gene which seems to be involved in autophagy and has an orthologue in the C. elegans genome.
Since RNAi did not allow to detect a clearcut phenotype in nematodes, we therefore generated a KO model by CRISPR/Cas9 technology. KO animals did not show a significant reduction in survival after starvation, but manifested a precocious aging phenotype with locomotion impairment and reduced lifespan compared to controls. We are currently performing further experiments to analyze the autophagic flux in absence of MYTHO and characterize the pathway linking this gene to the IGF/Akt/FOXO signaling.
A novel genetic variant has been identified in a gene that belongs to Crescerin1 family of proteins regulating microtubule dynamics, in patients with a Meckel-Gruber-like phenotype. The worm orthologue che-12 is expressed in the cilium of a subset of sensory neurons.
We generated worm lines harboring the novel missense variant found in patients by CRISPR/Cas9 technology. These were then characterized to explore potential effects on behaviors controlled by sensory neurons expressing che-12. We did not observe an impairment in chemotaxis ability on a NaCl gradient, nor a strong reduction of lipophilic dye-uptake frequency, however preliminary results indicate that the cilium of sensory neurons is shortened in che-12 knock-in mutants. The demonstration of the pathogenic effect of the variant could establish an important link between mutations in this gene (that has not been so far associated with a human disease) and ciliopathies.
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Stear, Jeffrey Hamilton. "Studies of chromosome structure and movement in C. elegans /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/5056.
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Hui, Ka Yi. "Cellular basis of ray morphology abnormal in C. elegans /." View abstract or full-text, 2009. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202009%20HUI.
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Grewal, Parwinder Singh. "Studies on saprobic rhabditid nematodes and their associated bacteria affecting mushroom culture." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46322.
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Marsac, Roxane. "La déficience en Adénylosuccinate Lyase - de la déficience métabolique aux défauts musculaires en utilisant le Caenorhabditis elegans comme modèle animal." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0321.
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La voie de biosynthèse des purines est un réseau métabolique conservé de procaryotes à l'Homme, assurant l'homéostasie de l'ATP et du GTP. Les purines peuvent être synthétisées de novo, réutilisées ou produites par interconversion de métabolites existants à l'aide de la voie dite de recyclage. De plus, les intermédiaires peuvent agir en tant que métabolites signals régulant l'expression génique. Cette voie est bien caractérisée chez des micro-organismes tels la levure ou la bactérie, mais peu de choses sont connues chez les métazoaires. Différentes maladies sont associées à des déficiences enzymatiques de la voie de biosynthèse des purines conduisant à des anomalies neuro-musculaires, des comportements du spectre autistique et à un retard psychomoteur chez l'Homme. Nous nous sommes particulièrement intéressés à la déficience en Adénylosuccinate Lyase (ADSL), une enzyme impliquée dans la voie de novo et dans la voie de recyclage des purines, responsable des symptômes neuronaux et musculaires chez les patients.Pour mieux comprendre les mécanismes sous-jacents à cette déficience, nous avons établi C. elegans comme organisme modèle métazoaire pour étudier la voie de la biosynthèse des purines, et en particulier le déficit en ADSL. Dans notre étude, par alignement de séquence, profil HPLC et complémentation fonctionnelle chez la levure, nous avons montré que la voie de novo et la voie de recyclage sont fonctionnellement conservées chez C. elegans. Grâce à notre étude, nous sommes en mesure d’attribuer des phénotypes développementaux et tissus spécifiques à des étapes séparables du métabolisme des purines dans un organisme modèle métazoaire. Notre analyse montre que l'activité ADSL dans la voie de recyclage joue un rôle crucial pour le maintien de la lignée germinale, pour l'intégrité musculaire et pendant le développement post-embryonnaireThe purine biosynthesis pathway is a metabolic network conserved from prokaryotes to humans, ensuring ATP and GTP homeostasis. Purines can either be synthesized de novo, reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Moreover, intermediates can act as signal metabolites regulating gene expression. This pathway is well characterized in microorganisms such as heat or bacteria, but little is know about its regulation in metazoans. Different diseases are associated with deficiencies in purine synthesis enzymes leading to neuromuscular defects, autistic spectrum behaviors and psychomotor delay in humans. We focused our analysis on the deficiency of Adenylosuccinate Lyase (ADSL), which is an enzyme involved in the purine de novo and the recycling pathways causing neuronal and muscular symptoms in patients. To better understand mechanisms underlying this deficiency, we have established C. elegans as a metazoan model organism to study the purine biosynthesis pathway, specially the ADSL deficiency. In our study, by sequence alignment, HPLC profiling and functional complementation in yeast, we have shown that both the de novo and the recycling pathway are functionally conserved in C. elegans. Thanks to our study, we are able to ascribe developmental and tissue specific phenotypes to separable steps of the purine metabolism network in a metazoan model organism. Our analysis shows that ADSL activity in the recycling pathway plays a crucial role for germline maintenance, for muscle integrity and during the post-embryonic development
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Tran, Karen. "A Microfluidic Platform for Exploring Learning Behavior in C. elegans." Digital WPI, 2015. https://digitalcommons.wpi.edu/etd-theses/1245.
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"Microfluidic technologies are popular for biological research, enabling precise physical and chemical control of the microenvironment surrounding living cells and small organisms. Caenorhabditis elegans, a 1 mm long nematode, is capable of olfactory associative learning using the classical conditioning paradigm of pairing an unconditioned stimulus that elicits an innate response, such as food, with a second stimulus, such as an odor, which then elicits a learned behavioral response to this conditioned stimulus alone. Conventional chemotaxis assays on agar petri-plates have been widely used to observe behavioral changes indicative of associative learning; however, reproducibility of these behavioral assays is a major challenge. Here, we describe a microfluidic system that improves the reproducibility of chemotactic behavioral assays by providing better spatiotemporal control of stimuli, gentler worm handling, and more detailed behavioral quantification. Specifically, the microfluidic designs in this study present a uniform conditioning environment followed by a temporally stable linear odor gradient to assess changes to olfactory preference. Stimuli are presented in an enclosed environment to multiple worm populations whose locomotory patterns are analyzed using machine vision. Furthermore, we established an optimized protocol for a positive associative learning paradigm in which animals increase their preference for an odorant, butanone, when previously paired with bacterial food. We reproduced plate-based learning results in wild-type and learning-deficient genetic mutant animals, and demonstrated how developmental stages and chemicals alter the plasticity of olfactory preference. "
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Zhao, Yang. "G/C tracts and genome instability in Caenorhabditis elegans." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/936.
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The integrity of the genome is critical to organisms and it is affected by many factors. Radiation, for example, poses a serious threat to genome stability of human beings. While physical monitors for radiation hazard are present, the biological consequences of long term exposure to radiation are not well understood. With the opportunity as part of the International Caenorhabditis elegans Experiment-1 flight project, several approaches using C. elegans were taken to measure mutational changes that occurred during the spaceflight. Among these methods, the eT1 balancer system was demonstrated to be well-suited as an integrating biological dosimeter for spaceflight.
The dog-1 gene in C. elegans is required to prevent mutations at poly-G/poly-C tracts, and previous work has described that in the absence of DOG-1, small deletions initiate within these tracts, most likely as a consequence of improperly repaired replication blocks. The eT1 balancer system was adapted to investigate the broad mutational spectrum of dog-1 mutants. Using this system, I was able to determine a forward mutation rate of approximately 1 x 10-3, 10 fold higher than spontaneous. Both small deletions as reported previously and unreported large chromosome rearrangements were observed, and most of mutations analyzed are associated with G/C tracts. Thus, I propose that following dog-1-induced replication blocks, repair leads to a wide range of mutational events and chromosomal instabilities, similar to those seen in human cancers.
The existence of the G/C tracts in C. elegans creates a fortuitous but perplexing problem. They are hotspots for genome instability and need enzymatic protection. In the genome of C. elegans, approximately 400 G/C tracts exist and are distributed along every chromosome in a non-random pattern. G/C tracts are also over-represented in another Caenorhabditis species, C. briggsae. However, the positions and distribution differ from those in C. elegans. Furthermore, in C. elegans, analysis of SAGE data showed that the position of the G/C tracts correlated with the level of gene expression. Although being a threat to genome stability, the genomic distribution of G/C tracts in C. elegans and their effect on regional transcription levels suggest a role for G/C tracts in chromatin structure.
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Kaul, Aamna. "The mechanism of Ivermectin-induced cytotoxicity in C. elegans /." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82263.
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The anti-nematodal drug ivermectin hyperactivates invertebrate-specific glutamate-gated chloride channels (GluCls) causing pharyngeal paralysis and a cessation of feeding and growth. I find that for C. elegans even brief exposure to ivermectin can lead to irreversible pharyngeal paralysis. Ivermectin induces heterogeneous vacuolation in the pharynx that appears slowly and accumulates over several days. This vacuolation is almost completely rescued by a mutation in avr-15, which codes for the alpha-subunit of pharyngeal GluCls. The vacuoles stain strongly with Lysotracker Red and are therefore likely to be acidic compartments of the endosomal-lysosomal system. Examination of mutants defective for endocytosis (rme-1, rme-8, and cup-5) uncovers the presence of acidic vacuoles identical in appearance to ivermectin-induced vacuoles. Further, RME-1, a marker for recycling endosomes, is shown to redistribute soon after ivermectin exposure. Examination of the effects of ivermectin on extrapharyngeal neurons expressing ectopic avr-15 reveals an apoptotic phenotype that is shown to be ced-independent.
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Nolis, Thomas. "GFP-based screen for meiotic mutants in «C. elegans»." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66851.
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Meiosis causes the reduction of diploid cells into haploid gametes playing a significant role in all sexually reproducing organisms. The progression of meiosis can be broken down into two stages: meiosis-I and meiosis-II. In meiosis-I, homologous chromosomal segregation results in the formation of a chiasma – a secure connection between homologs. Establishing a chiasma requires three major landmarks between homologous chromosomes: recognition and alignment, synapsis, and recombination. A defect in any one of these key events can cause chromosomal non-disjunction or cell aneuploidy. The nematode Caenorhabditis elegans has many attributes that make it a well-suited model for studying various aspects of meiosis. The germ-line nuclei mature in a spatiotemporal manner, and the nuclei are easily distinguishable, during their progression of meiotic prophase-I, through DAPI staining. Should a mutation impair homologous chromosomal segregation of the X-chromosome the progeny of the animal will bear a visibly higher percentage of males, presenting a 'High Incidence of Males', or a 'Him', phenotype. The goal of this study is to screen, identify, and isolate more Him mutations by building on the screen "Green Eggs and Him". Nineteen Him mutants have been isolated, and 17 studied, in this project. DAPI staining has allowed the categorization of the mutants into: cell cycle, pairing, synapsis, or recombination defective mutants. Measuring autosomal and X-chromosome non-disjunction levels have allowed for an additional severity-level categorization for each of the seventeen mutations found. 4 mutations were found to be severe, 3 as severe/moderate, 2 moderate, 4 as moderate/low, and 4 were categorized as low-severity mutations. 9 of the 17 mutations were determined as having recombination deficiencies; 5 as pairing/synapsis defects – where the deficiency could be in just one of the processes, or compounded in both;La méiose cause une réduction de chromosomes diploïdes dans les gamètes qui sont haploïde, jouant un rôle significatif dans tous organismes qui se reproduisent sexuellement. La progression de méiose peut être séparée en deux étapes : méiose-I et méiose-II. En méiose-I, la ségrégation chromosomique des homologues a pour résultat la formation d'un chiasma – une connexion assurée entre homologues. Etablir un chiasma exige trois événements majeures entre les chromosomes homologues : la reconnaissance et l'alignement, le synapse, et la recombinaison. Un défaut dans n'importe lequel de ces événements clés peuvent causer la non-disjonction des chromosomes ou l'aneuploïdie de la cellule.Le nématode Caenorhabditis elegans a beaucoup d'attributs qui le favorise comme un modèle pour étudier des aspects divers de la méiose. Les noyaux des cellules germinales mûrissent d'une manière spatiotemporale, et les noyaux sont facilement identifiables pendant la progression de prophase-I avec un traitement DAPI. Si une mutation diminue la ségrégation des homologues du chromosome X, la progéniture de l'animal comptera un pourcentage élevé de mâles, présentant un phénotype « Lui ».L'objectif de cette étude est de trier, identifier, et isoler des mutations « Lui » avec le criblage « Oeufs Verts et Lui ». Dix-neuf mutants « Lui » ont été isolé, et dix-sept étudié, dans ce projet. Le traitement avec DAPI a permis la catégorisation des défauts des mutants dans une des catégories suivantes: le cycle cellulaire, l'union des homologues, le synapse, ou la recombination. La mesure des taux de non-disjonction des autosomes comparé à celui pour le chromosome X a permis une catégorisation supplémentaire des dix-sept mutations par rapport à leur sévérité. Quatre mutations sont sévères, trois sont sévères à modérées, deux sont modérées, quatre sont modérées à fa
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Shen, Michael Milton. "Genetic and molecular analysis of C. elegans male development." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254202.
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Lightfoot, James William. "The roles of SCC-2 during C. elegans meiosis." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.554218.
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Cohesin mediates sister chromatid cohesion (SCC), and its regulated association with chromatin is required to promote faithful chromosome segregation during mitosis and meiosis, as well as for the efficient repair of DNA double strand breaks (DSBs). In the mitotic cell cycle loading of cohesin requires a conserved complex containing the Scc2INipbl protein, which has also been proposed to promote binding of the cohesin-related complexes condensin and SMC-5/6. However, little is known about the factors that promote loading of cohesin and related SMC (structural maintenance of chromosomes) complexes during meiosis. During a screen for meiotic mutants in C. elegans, I isolated an allele of sec- 2, scc-2 (jql), that has allowed me to determine the roles that SCC-2 plays during meiosis. I show that during C. elegans meiosis loading of cohesin, but not condensin 11 or SMC-5/6, requires SCC-2, demonstrating that loading of condensin 11 and SMC-5/6 can be achieved by mechanisms independent of both SCC-2 and cohesin. The lack of cohesin in scc-2 mutants impairs the repair of meiotic DSBs and recombination intermediates accumulate extensively. Surprisingly, these accumulated intermediates fail to induce an apoptotic response, which is the normal outcome when persistent DNA lesions are detected by the conserved pachytene DNA damage checkpoint. I observed that this defect is caused by a failure to load the DNA damage sensor 9-1 ~ I complex onto persistent recombination intermediates in scc-2 mutants. A lack of meiotic cohesin also impairs the timely loading of the RAD-51 recombinase to irradiation-induced DSBs. These findings suggest that meiotic cohesin is required in the early steps of DSB processing and for the recruitment of checkpoint proteins to sites of DNA damage, thus revealing novel roles for cohesin.
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Zhuang, Jimmy Jiajia. "Phenotypes and genetic mechanisms of C. elegans enhanced RNAi." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:10758.
Full textAbstract:
RNA interference (RNAi) potently and specifically induces gene knockdown, and its potential for reverse genetics in Caenorhabditis elegans is enormous. However, even in these nematodes, RNAi can be induced more effectively via enhanced RNAi (Eri) mutant backgrounds. With advances in small RNA sequencing, evidence has suggested that the eri pathway plays an endogenous gene regulatory role, which competes with experimentally introduced RNAi triggers for limiting resources. However, the nature, cellular location, and physiological consequences of this small RNA pathways competition remain unclear. To answer these questions, I first fully characterized the genetic phenotypes of all known Eri mutants. I discovered that different components of the eri pathway have subtle differences upon mutation, which affects more than exogenous RNAi. I then attempted to screen for novel enhanced RNAi mutants, guided by hypothetical mechanisms or tissues of expression not associated with known mutants. After these attempts, I fully characterized the genetic mechanisms that account for enhanced RNAi. Surprisingly, I discovered that the nuclear Argonaute nrde-3 and the peri-nuclear P-granule component pgl-1 are necessary and sufficient for an Eri response. Finally, I examined the impact of the competition among microRNA, endogenous siRNA, and exogenous RNAi pathways. I discovered that C. elegans develops slower upon perturbations to its normal flux of small RNA pathways. Insights from these phenotypes and genetic mechanisms shed light on the importance of small RNA biology and offer a novel suite of tools for sensitizing RNAi in broader contexts, especially given the deep evolutionary conservation of most eri-associated genes.