Developing dynamic biosensors for measuring G protein-coupled receptor (GPCR) signalling pathways, for high-throughput drug screening.

高度调控的细胞内信号传导是生理的基础，而异常的信号传导途径与许多病理有关。控制这些途径的细胞膜受体的药物操作有助于治疗。这些受体中最大的家族是G蛋白偶联受体（gpcr）， FDA批准的药物中有很大一部分是针对这种受体的（截至2017年为33%）。两个熟悉的靶向gpcr的例子包括分别用于治疗过敏和高血压的组胺和β -肾上腺素能受体。GPCR家族的成员被多种内源性激动剂激活，从肽和小分子到离子甚至光子。它们的作用是将整个细胞外刺激范围转化为细胞内的生化级联反应，从而改变细胞生理学。为此，激动剂结合受体激活异源三聚体G蛋白，该蛋白具有多种不同的效应，通常会导致靶基因转录。

Highly regulated intracellular signalling underpins physiology, whereas aberrant signalling pathways are associated with many pathologies. Pharmaceutical manipulation of the cell membrane receptors that govern such pathways is instrumental to therapeutics. The largest family of these receptors are G protein-coupled receptors (GPCRs), for which a high proportion of drugs approved by the FDA act on (33% as of 2017). Two familiar examples of targeted GPCRs include the histamine and beta-adrenergic receptors for the treatment of allergies and hypertension, respectively. Members of the GPCR family are activated by a diverse range of endogenous agonists, spanning from peptides and small molecules to ions and even photons. They serve to transduce this whole gamut of extracellular stimuli into intracellular biochemical cascades that alter cellular physiology. To do this, agonist bound receptors activate heterotrimeric G proteins, which can have a multitude of different effectors and commonly result in target gene transcription.