My research aims to understand the folding and function of the hormone leptin with the long- term-goal of understanding its role in the gut-brain axis. Diet is one of the principal and most intimate interfaces that animals have with the environment. The environmental input and the host may stress the gut microbiota, which in turn affect post translational modification of host proteins important in animal health. The hormone leptin, best known for its role in obesity and diabetes, is hypothesized to be the link between nutritional status and the gut microbiome. Our interdisciplinary research utilizes a combination of Molecular Dynamics (MD) simulations, in vitro biophysical characterization combined with in cell and in vivo assays to understand the mechanism of leptin signaling. As such, these studies promise to provide both the very basic biology associated with the leptin signaling 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.