Multi-colour single molecule fluorescence-based analysis of native G protein-coupled receptor organization

G蛋白偶联受体（GPCR）是存在于人类和其他动物大多数细胞表面的蛋白质。这些蛋白质检测溶液中的光和分子，在细胞内产生信号，告诉它已经检测到特定的物质。这些信号构成了我们视觉和味觉的基础，并调节我们的情绪和行为。GPCR是由人类基因组编码的最大的细胞受体组，并且是目前临床使用的一半以上药物的靶标。因此，正确理解这些分子如何发挥其作用至关重要。由于缺乏足够灵敏的方法来检测活细胞上的单个蛋白质，许多重要的研究尚未进行。我们已经开发了一种基于荧光的显微镜方法，我们已经证明该方法具有必要的灵敏度来分析活细胞上的单个蛋白质。我们打算使用这种新方法来解决一些关于GPCR的结构和行为的关键问题。特别是，我们将确定受体在细胞表面的组织方式，以及当GPCR检测溶液中的分子时受体的变化方式。这些问题是整个气相化学还原生物学领域最具争议的问题之一。这项研究有可能从根本上改变我们对这些分子如何工作的想法。

G-protein coupled receptors (GPCRs) are proteins present on the surfaces of most cells in humans and other animals. These proteins detect both light and molecules in solution, producing signals inside the cell that tell it that the particular substance has been detected. These signals form the basis of our sense of sight and taste as well as regulating our mood and behaviour. The GPCRs are the largest group of cellular receptors encoded by the human genome, and are the targets for more than half the drugs presently in clinical use. It is, therefore, of the utmost importance to properly understand how these molecules exert their effects. Many important studies have not been performed due to the lack of sufficiently sensitive methods to detect individual proteins on live cells. We have developed a fluorescence-based microscopic method, which we have shown to have the necessary sensitivity to analyse individual proteins on live cells. We intend to use this new method to address some of the key questions about the structure and behaviour of GPCRs. In particular, we will determine how the receptors are organised on the cell surface and how this changes when GPCRs detect molecules from solution. These questions are among the most contentious in the entire field of GPCR biology. This research has the potential to fundamentally change our thinking about how these molecules work.