My research aims to understand how the hormone leptin folds into its 3-dimensional structure to function and how it interacts with its receptor, which links this hormone to its critical biological role controlling energy expenditure. Furthermore, leptin is best known for its role in obesity and diabetes in humans but is also hypothesized to be the link between nutritional status and the gut microbiome. To understand the molecular details of the folding and function of leptin and its receptor, we use spectroscopic methods including tryptophan fluorescence, circular dichroism (CD), and nuclear magnetic resonance (NMR) in combination with molecular dynamics (MD) simulations to characterize functional properties. Combined with in vivo studies, in collaboration with Dr Joanne Yew at the Pacific Biosciences Research Center School of Ocean and Earth Sciences and Technology, we are using the fruit fly D. melanogaster as a model system to provide a window into the degree of evolutionary conservation in activity and function of the LEP-R complex.
Combined with in vitro studies of both the human and drosophila signaling complex, my ICEMHH pilot project will glean information on the biophysical properties governing the formation of the active signaling complex for controlling energy expenditure. As such, these studies promise to provide both the very basic biology associated with this complex, as well as provide insights into those characteristics of the complex that would be valuable targets for therapeutics for human diseases, such as obesity.
Integrative Center for Environmental Microbiomes and Human Health