Understanding endogenous allosteric modulators of G protein-coupled receptors

主要的生命科学挑战包括细胞外的化学物质如何向细胞内的蛋白质发出信号，这如何导致生理反应，以及这些过程的功能障碍如何导致病理生理学。尽管G蛋白偶联受体（GPCRs）至关重要，但关于内源性和合成分子对它们的调节仍有许多有待了解。该项目旨在解决这一差距，通过建立在最近已经进行的突破性研究，通过专注于GPCR的替代结合位点，称为变构位点。主要的假设是，这些变构位点在GPCR中广泛存在，因为身体产生内源性变构配体，这些配体在很大程度上仍未被识别，但在生物学中发挥着重要作用。

Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.