? 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 of the 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 energy balance in C. elegans?"""""""" I have identified a few key genes that are important for serotonin fat regulation in C. elegans. Using a combination of behavioral and physiological assays, I will examine the roles of these newly-identified genes in food intake and energy expenditure. Together with molecular and genetic analyses, I aim to specify the serotonergic network that couples food sensation to changes in feeding regulation and energy 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 work proposed here lays the foundation upon which I will embark as an independent investigator at an academic research institution in the next two years. My current environment at the University of California-San Francisco under the mentorship of Dr. Kaveh Ashrafi and Dr. Keith Yamamoto, is ideally suited for my scientific and professional interests. 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. ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Career Transition Award (K99)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Haft, Carol R
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Srinivasan, Supriya; Sadegh, Leila; Elle, Ida C et al. (2008) Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms. Cell Metab 7:533-44