Exploiting metabolite GPCR mechanotransduction to find new treatments for metabolic disorders

利用代谢物 GPCR 机械转导寻找代谢紊乱的新疗法

• 批准号: 2885713
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2885713
• 关键词: Exploiting; metabolite; GPCR; mechanotransduction; find

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.

GPCR 是最大的膜蛋白家族和最成功的药物靶点。最近，一组代谢物传感 GPCR 引起了人们对治疗代谢性疾病（包括肥胖和糖尿病）的兴趣。在这些疾病中，脂肪组织发生显着重塑，导致组织机械性能的变化。尽管之前的工作已经证明许多 GPCR 的功能会因机械刺激而改变，但人们对脂肪中的这些机械变化如何影响代谢物 GPCR 的功能知之甚少。该项目将使用先进的显微镜技术首先确定代谢物 GPCR 的操作如何影响脂肪细胞的机械特性。然后，它将确定这些机械特性的变化如何改变受体的信号传导曲线。最后，这些信息将用于设计用于药物筛选的新型细胞模型，以正确解释代谢紊乱中发生的脂肪组织机械特性的变化。