ADAPTATION AND SURVIVAL OF THE NEMATODE Caenorhabditis elegans DURING OSMOTIC-ANOXIC STRESS

Abstract

Oxygen is an absolute requirement for multicellular life. Animals that are deprived of oxygen for sufficient periods of time eventually become injured and die. This is largely due to the fact that, without oxygen, animals are unable to generate sufficient quantities of energy. In human diseases triggered by oxygen deprivation, such as heart attack and stroke, osmotic stress and cell swelling (edema) arise in affected tissues as a direct result of energetic failure. Edema independently enhances tissue injury in these diseases by incompletely understood mechanisms, resulting in poor clinical outcomes. This dissertation presents investigations into the effects of osmotic stress during complete oxygen deprivation (anoxia) in the genetically tractable nematode Caenorhabditis elegans. In these investigations, it is shown that osmotic stress promotes tissue swelling and reduces animal survival during anoxia. In addition, several genetic pathways, including insulin-like signaling and aquaporin-mediated water transport, are identified that affect survival in this environment. These pathways are shown to impact the ability of the nematode to store and utilize glycogen, providing evidence that energetic supply and demand are factors for nematode survival of osmotic-anoxic stress.