Analyses of diverse stresses, including hypoxia, cyanide, and hypergravity in Caenorhabditis elegans

Organisms often encounter various forms of stress during their lifespan. The response to stress involves the regulation of cellular processes by stress response modulators that function to ultimately enable resistance and survival. In this dissertation I used Caenorhabditis elegans as a model to study the effects of a variety of stresses including the response to cyanide, hypoxia, and hypergravity. Chapter 2 of this thesis focuses on understanding the mechanisms of cyanide resistance in C. elegans. We employed a novel microfluidic device to describe the resistance phenotypes with greater spatio-temporal resolution. The results shed light on the underlying genetic bases that contribute to cyanide resistance, including the role of the hypoxia-inducible factor HIF-1. They also reveal new findings about the cyanide resistance phenotype, and help establish the applicability of microfluidic devices in studying the effects of aqueous toxicants in real-time. Chapter 3 is a study investigating the crosstalk between the stress response modulators HIF-1, DAF-16, and HLH29 in C. elegans. We found significant over-representation of DAF-16 target genes, as well as HLH29 target genes in our lists of genes up- or down- regulated by hypoxia or in animals with over-active HIF-1. Genes identified in this study are known to play important roles in the response and resistance to diverse forms of stress. The findings from this study illustrate the complex mechanisms employed by cells to regulate the expression of subsets of genes in the response to specific forms of stress. In chapter 4 we studied the effects of hypergravity exposure on C. elegans mobility, behavior, reproduction, and lifespan. We found that the animals rapidly recoverered mobility after short, intense bouts of hypergravity exposure, but their reproductive capabilities and lifespans were altered after longer durations of treatment. The results suggest that long term exposure to stress in the form of hypergravity may be detrimental to the animal\u27s health and physiology. Collectively, the results from my thesis help elucidate the important roles played by stress response mediators in contributing to an organism\u27s survival. They also illustrate the rich and complex ways in which organisms modulate their responses to various forms of stress