Exploiting metabolite GPCR mechanotransduction to find new treatments for metabolic disorders

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GPCRs are the largest family of membrane proteins and most successful drug targets. Recently a group of metabolite sensing GPCRs has attracted interest in the treatment of metabolic disorders, including obesity and diabetes. In these disorders significant remodeling of adipose tissue occurs, leading to changes in the mechanical properties of the tissue. Although previous work has demonstrated that the function of many GPCRs is altered by mechanical stimuli, very little is known about how these mechanical changes in adipose affect the function of metabolite GPCRs. This project will use advanced microscopy techniques to first define how manipulation of metabolite GPCRs affects the mechanical properties of adipocytes. It will then establish how these changes in mechanical properties alter the signaling profiles of the receptors. Finally, this information will be used to engineer novel cell models for drug screening that properly account for changes in the mechanical properties of adipose tissue that occur in metabolic disorders.