To ensure survival, animals must constantly assess food status in the environment, and respond appropriately by matching food intake to energy expenditure. The net balance between the two is reflected in the fat stores ofthe animal. The neurotransmitter serotonin plays a central role in maintaining this dynamic balance, by relaying food signals from the environment to elicit changes in behavior and physiology of the animal so that fat homeostasis is maintained. The goal of the research proposed here is to address the question: """"""""How does serotonin signaling modulate enerqv balance in C. elegans?"""""""" In forward genetic and RNAi screens, I have identified several genes that are important for serotonergic fat regulation in C. elegans. Using a combination of behavioral and physiological assays, I will examine the roles ofthese newly-identified genes in food intake, energy expenditure and other measures of energy balance. Together with molecular and genetic analyses, I aim to specify the serotonergic expenditure in C. elegans. My current research objectives are well-aligned with my long-term interest in understanding how the environment influences complex behavior and physiology at the organismal level. Understanding the complex intersection of genetics and environment is a frontier in the biological sciences with major, direct impacts on human health.
The de-regulation of energy balance leads to obesity, a rising health concern world-wide. Indeed, current estimates suggest that more than 30% of Americans are obese, a condition that is a prime risk factor for cardiovascular disease, diabetes and reduced life expectancy. The ancient conservation of serotonin function in many species including mice and humans suggests that work proposed here will provide novel genetic targets for the study of body fat regulation.
| Noble, Tallie; Stieglitz, Jonathan; Srinivasan, Supriya (2013) An integrated serotonin and octopamine neuronal circuit directs the release of an endocrine signal to control C. elegans body fat. Cell Metab 18:672-84 |
