Genetic basis of diet-dependent responses across the lifespan

点击翻译按钮获取中文摘要

Project Summary: C. elegans respond to changes in food availability, environmental conditions, and bacterial diets through nervous system integration of sensory information and coordinated behavioral, physiological, and metabolic responses12, 13, 14. The laboratory and natural environments of C. elegans differ drastically in the bacterium present – the laboratory environment relies on monocultures of E. coli, while the natural environment exposes C. elegans to a wide variety of bacterial species including Bacteroidetes, Proteobacteria, and Actinobacteria1, 2. My recently published study takes advantage of bacterial diets found in both C. elegans natural and laboratory environments and provides a comprehensive assessment of changes in physiology and transcriptomic signatures as a result to simply changing the bacteria diet worms were propagated on3. To my knowledge, this paper was the first head-to-head comparison demonstrating how the natural environment controls physiology incongruously to that of the laboratory environment, however, I realized that this study is just the beginning of understanding the multiplexed relationship between dietary exposure and life history traits. The overarching goal of this proposal is to reveal novel mechanisms of the complex food-based decision making to elucidate the underlying genetic basis of diet-dependent responses across the lifespan. With two main approaches, I plan to take advantage of the amenable C. elegans model and examine how two distinct physiological attributes, development and food choice, can be differentially impacted by dietary exposure to lifespan-promoting bacteria. The first aim will be to identify the neurocircuitry involved in deciding between two bacterial diets by developing unbiased food choice assays (1a). With the use of these assays, I plan to identify the olfactory pathways involved with a combination of neuronal ablation and genetic mutants (1b). Finally, I will examine how these mutations in the olfactory pathways will influence C. elegans adaptive capacity and the multiple aspects of physiology that converge upon aging and lifespan (1c). My second aim relies on genetics to examine how bacterial diet controls normal progression of development. I plan to approach this aim by identifying developmentally slow mutants generated by an ethyl methanesulfonate screen in order to reveal novel genetic regulators of developmental timing (2a). Due to the high conservation of signaling pathways involved in dietary response, these studies will reveal new insights into impacts diet has on health on longevity and stimulate future studies to use food as a nutraceutical to combat the onset of aging and diseases.