The primary storage carbohydrate in animal tissue is glycogen. The deposition and utilization of glycogen is controlled by many internal and external factors, including diet, activity level, hormonal signals, and intracellular processes. We present here the results of a genome-wide RNAi screen for genes that influence glycogen storage in Caenorhabditis elegans. The results indicate that when particular biological processes are interrupted, such as respiration or protein synthesis, a consistent glycogen storage phenotype will develop. We go on to establish the importance of hexosamine-based nutrient sensing in controlling nematode glucose uptake and glycogen storage, and demonstrate that the results of our screen can be used to identify novel genes that interact with nutrient sensing, which may be informative for understanding the development of complex metabolic diseases, such as diabetes. Another aspect of glycogen metabolism is the role it plays in allowing animals to adapt to changing environmental conditions, which is essential to the fitness of organisms. In some cases, adaptation of the parent alters the offspring's phenotype. Such parental effects are adaptive for the offspring if the future environment is similar to the current one, but can be maladaptive otherwise. Here we show that exposing adult Caenorhabditis elegans to hyperosmotic conditions protects their offspring from the same, but causes sensitivity to anoxia exposure. We show that this alteration of survival is correlated to changes in the sugar content of adults and embryos and that those genetic backgrounds which affect sugar homeostasis also alter the ability of embryos to survive in hyperosmotic and anoxic conditions and engage in the adaptive paternal effect. Our results indicate that there is a physiological trade-off between the presence of glycerol, which protects animals from hyperosmotic conditions, and glycogen, which is consumed during anoxia. These two metabolites play an essential role in the survival of worms in these adverse environments, and the adaptive parental effects we describe are mediated through the provisioning of these metabolites to the embryo.
|Advisor:||Roth, Mark B.|
|School:||University of Washington|
|School Location:||United States -- Washington|
|Source:||DAI-B 71/10, Dissertation Abstracts International|
|Subjects:||Molecular biology, Genetics, Physiology|
|Keywords:||Caenorhabditis elegans, Carbohydrates, Glycogen, Hypoxia, Osmotic stress, Survival|
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