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Author: Jimmy Jiajia Zhuang
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
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.
Author: Jimmy Jiajia Zhuang
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
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.
Author:
Publisher: Academic Press
ISBN: 9780123969682
Category : Science
Languages : en
Pages : 0
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Book Description
This new volume of Current Topics in Developmental Biology covers developmental timing, with contributions from an international board of authors. The chapters provide a comprehensive set of reviews covering such topics as the timing of developmental programs in Drosophila, temporal patterning of neural progenitors, and environmental modulation of developmental timing.
Author: Victoria Vu
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
A common problem in the study of human disease genetics is that the severity of symptoms can vary greatly between individuals, even when the underlying disease mutations are identical. Natural variation in genetic background is recognized as one of the contributors to variation in phenotype severity, but our understanding of the underlying mechanisms is limited. Here, I endeavour to explore why differences in genetic background lead to phenotypic variations by systematically examining a large set of single-gene perturbations in Caenorhabditis elegans. In the first section of this thesis, I broadly examine the effect of genetic background on these perturbed phenotypes employing RNAi in two C. elegans isolates, the canonical lab strain N2 and a commonly used wild-type CB4856 for comparison. This screen yielded 120 genes that produced a more severe phenotype in N2 and 127 genes that produced a more severe phenotype in CB4856 (p-value ≤0.05), with notable enrichments in specific functional groups. These differences in phenotypic severity are recapitulated in both genetic mutants and animals chemically treated to perturb the same functional networks. In the latter part of my thesis, I explore the genetics of variation in perturbed phenotypes and find that they are complex, affected by both the expression level of the gene itself and that of genes within the same functional group. For instance, a gene that has lower expression in N2 will likely exhibit a more severe phenotype in N2, and experimentally lowering the gene expression of the gene itself or genes within the same functional group will increase the severity of the phenotype. I further explore the genetics underlying the phenotypic variation of a subset of these gene perturbations using quantitative trait loci (QTL) mapping. With this approach, I identified a broad trend of four QTLs that repeatedly underlie the phenotypic variations in a set of functionally unrelated genes and that most perturbation variations between N2 and CB4856 have more than one underlying genetic cause. Together, these data show that genetic backgrounds frequently modify perturbed phenotype severities and that the genetics underlying this variation is complex.
Author: Maurice David Butler
Publisher:
ISBN:
Category :
Languages : en
Pages : 218
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Book Description
RNA interference (RNAi) was formally described in Caenorhabditis elegans ( C. elegans ) as the process by which long double-stranded RNA (dsRNA) post-transcriptionally induces potent silencing of an endogenous gene that is homologous to the trigger. We now understand RNAi-related silencing mechanisms to function in endogenous processes throughout phylogeny. The inability of RNAi to target specific genes and tissues has raised questions about the molecular and evolutionary basis for these limitations. This dissertation describes an investigation into genes whose wild-type function is to restrict the potency of exogenous RNAi in C. elegans. Genetically screening for mutants displaying an enhanced response to exogenous dsRNAs, we isolated mutations in genes encoding known interactors of the central player of small-RNA-mediated pathways--the endoribonuclease Dicer--which all exhibit pleiotropic phenotypes such as sterility. We focused on non-sterile mutants from the screen, with the expectation that they would outline a novel mechanism for the negative regulation of RNAi. The non-sterile mutants define at least five genes.
Author: Jerry J. Buccafusco
Publisher: CRC Press
ISBN: 1420041819
Category : Medical
Languages : en
Pages : 341
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Book Description
Using the most well-studied behavioral analyses of animal subjects to promote a better understanding of the effects of disease and the effects of new therapeutic treatments on human cognition, Methods of Behavior Analysis in Neuroscience provides a reference manual for molecular and cellular research scientists in both academia and the pharmaceutic
Author: Robert F. Schleif
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 724
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Book Description
In the first edition of Genetics and Molecular Biology, renowned researcher and award-winning teacher Robert Schleif produced a unique and stimulating text that was a notable departure from the standard compendia of facts and observations. Schleif's strategy was to present the underlying fundamental concepts of molecular biology with clear explanations and critical analysis of well-chosen experiments. The result was a concise and practical approach that offered students a real understanding of the subject. This second edition retains that valuable approach--with material thoroughly updated to include an integrated treatment of prokaryotic and eukaryotic molecular biology. Genetics and Molecular Biology is copiously illustrated with two-color line art. Each chapter includes an extensive list of important references to the primary literature, as well as many innovative and thought-provoking problems on material covered in the text or on related topics. These help focus the student's attention of a variety of critical issues. Solutions are provided for half of the problems. Praise for the first edition: "Schleif's Genetics and Molecular Biology... is a remarkable achievement. It is an advanced text, derived from material taught largely to postgraduates, and will probably be thought best suited to budding professionals in molecular genetics. In some ways this would be a pity, because there is also gold here for the rest of us... The lessons here in dealing with the information explosion in biology are that an ounce of rationale is worth a pound of facts and that, for educational value, there is nothing to beat an author writing about stuff he knows from theinside."--Nature. "Schleif presents a quantitative, chemically rigorous approach to analyzing problems in molecular biology. The text is unique and clearly superior to any currently available."--R.L. Bernstein, San Francisco State University. "The greatest strength is the author's ability to challenge the student to become involved and get below the surface."--Clifford Brunk, UCLA
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309171806
Category : Nature
Languages : en
Pages : 347
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Book Description
Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.
Author: Joan Marsh
Publisher: John Wiley & Sons
ISBN:
Category : Medical
Languages : en
Pages : 344
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Book Description
Connects classical cellular descriptive studies with more recent work on the molecular and genetic aspects regarding germline development. Prominent scientists discuss research on a range of organisms including insects, worms, birds, fish, amphibia, mammals and green algae. Specification of germ cells, their migration to the gonads and subsequent interactions with the soma and evolutionary factors of their segregation are among the topics covered.
Author: Henry F. Epstein
Publisher: Academic Press
ISBN: 0125641494
Category : Caenorhabditis elegans
Languages : en
Pages : 687
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Book Description
The first of its kind, this laboratory handbook emphasizes diverse methods and technologies needed to investigate C. elegans, both as an integrated organism and as a model system for research inquiries in cell, developmental, and molecular biology, as well as in genetics and pharmacology. Four primary sections--Genetic and Culture Methods, Neurobiology, Cell and Molecular Biology, and Genomics and Informatics--reflect the cross-disciplinary nature of C. elegans research. Because C. elegans is a simple and malleable organism with a small genome and few cell types, it provides an elegant demonstr.
Author: Timothy G. Geary
Publisher: Springer Science & Business Media
ISBN: 1441969020
Category : Medical
Languages : en
Pages : 246
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Book Description
The need to continually discover new agents for the control or treatment of invertebrate pests and pathogens is undeniable. Agriculture, both animal and plant, succeeds only to the extent that arthropod and helminth consumers, vectors and pathogens can be kept at bay. Humans and their companion animals are also plagued by invertebrate parasites. The deployment of chemical agents for these purposes inevitably elicits the selection of resistant populations of the targets of control, necessitating a regular introduction of new kinds of molecules. Experience in other areas of chemotherapy has shown that a thorough understanding of the biology of disease is an essential platform upon which to build a discovery program. Unfortunately, investment of research resources into understanding the basic physiology of invertebrates as a strategy to illuminate new molecular targets for pesticide and parasiticide discovery has been scarce, and the pace of introduction of new molecules for these indications has been slowed as a result. An exciting and so far unexploited area to explore in this regard is invertebrate neuropeptide physiology. This book was assembled to focus attention on this promising field by compiling a comprehensive review of recent research on neuropeptides in arthropods and helminths, with contributions from many of the leading laboratories working on these systems.
