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Nutrient Response and Aging in Invertebrate Models
[Thesis]. Manchester, UK: The University of Manchester; 2013.
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Abstract
The diet an organism keeps is crucial in sustaining its health and fitness. The fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans are excellent models for nutritional studies due to their small size, large progeny numbers, quick development, and modifiable laboratory diets. Here I examine these two organisms in order to better understand the complex interrelationship between an animal and its diet. Previous work has shown that in the wild numerous organisms are capable of selecting specific nutrients in a non-random manner in order to maximize fitness. However, the genetic underpinnings driving these nutrient choices remain elusive. Female fruit flies consume higher levels of protein following mating to prepare for the costs of reproduction. I examined the role of S6 Kinase (S6K), a downstream effector of the nutrient-responsive target of rapamycin pathway, in mediating this decision. I demonstrate that neuronal S6K activity and serotonin are involved in regulating protein consumption when allowed to choose nutrients freely as well as following macronutrient deprivation; suggesting that they may play a role in mediating postmating dietary switch and maintaining nutrient balance. Modulating levels of dietary components can have extensive impacts on processes such as development, fecundity, and metabolism in multiple organisms. However, the influence of dietary genetics on the consumer is virtually unknown. I performed a screen feeding single-gene mutants of E. coli to C. elegans and monitored the effects on the insulin-like signalling pathway (ILS). When mutated, genes involved in multiple processes and functions in E. coli enhanced activity of the ILS downstream transcription factor, DAF-16. One mutant strain of E. coli I pursued had a knockout of the cAMP-producing, adenylate cyclase gene. Addition of exogenous cAMP to the diet containing live, metabolically active E. coli rescued all the effects of the mutant on C. elegans; thereby suggesting that bacterial metabolism of dietary cAMP can influence the C. elegans ILS. Collectively, my work demonstrates how the nutrient-sensing pathways of the consumer can shape and be shaped by interactions with its diet. These studies contribute to a better understanding of the consumer-diet relationship, and could help guide future work to investigate the role of diet in disease, quality of life, and longevity.