General Biology Seminar

Abstract: Diet can have a significant impact on development and physiology. However, critical diet-derived effecter molecules and their precise molecular functions have not been fully elucidated. The nematode C. elegans uses bacteria as a food source and different bacterial strains can elicit distinct effects on developmental rate, lifespan, fertility, and gene expression, independently of caloric content. To begin to understand the molecular basis for this we compared to the standard laboratory diet of E. coli OP50 to other bacterial diets. Strikingly, we observed that the Comamonas diet increased growth rate, decreased brood size and shortened lifespan, compared to E. coli diets. Although growth acceleration in response to some diets has been demonstrated to occur via TOR-mediated mechanisms, we found that accelerated growth in response to a Comamonas diet occurs independent of TOR and Insulin nutrient sensing pathways. Gene expression profiling of animals grown on different diets revealed a number of genes whose expression is modulated in response to diet. Using the promoter of one gene whose expression is turned off in response to Comamonas (acdh-1), we created a GFP reporter strain to study the response to the Comamonas diet. With this reporter, we performed forward genetic screens and identified mutations in both the bacteria and the worm that abrogate this response. We identified metabolic pathways whose proper function is required to turn off expression on the Comamonas diet as well as transcriptional regulators required to maintain expression of this reporter on the E. coli diet. These findings reveal novel mediators of dietary response and uncover links between metabolic and transcriptional networks.