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

点击翻译按钮获取中文摘要

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.