Probing the hidden secrets behind G-protein Coupled Receptor dimerization

生物学中最重要的问题之一是了解细胞是如何感知环境的。G蛋白偶联受体(GPCRs)超家族已被证明是帮助细胞实现这一目标的主要参与者。最近的结构数据表明，GPCRs有不同的配体调节的信号状态，高阶低聚物对活性很重要，这表明GPCRs不是单一的开/关开关。相反，目前的假设是GPCR在一个复杂的同质和异构体阵列中工作，这些同质和异构体与它们的细胞环境相适应。GPCR功能最具争议的方面是不同GPCRs家族的成员如何相互作用形成所谓的异构体。这个项目的总体目标是了解GPCR异构体如何在这些受体阵列中发挥作用的分子和细胞机制，以帮助细胞感知他们的环境。完成这一博士学位后，你将精通四个主要领域(1)多肽的化学合成(2)活细胞中受体蛋白的可视化/量化(3)细胞信号和药理学以及(4)蛋白质生物化学。

One of the most important questions in biology is to understand how cells sense their environment. The G-protein coupled receptor (GPCRs) superfamily has been shown to be a major player in helping cells accomplish this. Recent structural data show that GPCRs have different ligand-modulated signalling states, and that higher order oligomers are important for activity, suggesting that GPCRs are not single on/off switches. Instead, the current hypothesis is that GPCRs operate in a complex array of homo- and heteromers tuned to their cellular environment. The most controversial aspect of GPCR function is how members of different families of GPCRs interact with each other to form so called heteromers. The overall objective of this project focuses on understanding the molecular and cellular mechanisms of how GPCR heteromers function within these receptor arrays to help cells sense their environment. Upon completion of this PhD you will become well versed in four major areas (1) chemical synthesis of peptides (2) visualisation / quantification of receptor proteins in live cells (3) cell signalling and pharmacology and (4) protein biochemistry.