FOR 2149: Elucidation of Adhesion-GPCR Signalling

粘附型G蛋白偶联受体形成一大类七跨膜(7TM)受体。7TM接收器已被证明是无数生理功能的关键，也是现代药物干预的宝库。黏附-GPCR似乎与7TM受体超家族的其他成员形成了鲜明的对比，因为他们是迄今为止最不了解的7TM受体类别。该研究组的科学目标集中在粘附性GPCR生物学中与其信号的生理和药理学特征有关的几个基本方面，包括它们的机械传感器的作用，作为它们被激活的信号转导步骤的系链激动性的存在，通过粘附性GPCRs控制的非典型信号的分析及其对细胞骨架动力学的影响。此外，研究股努力解构粘附性GPCRs对肿瘤和炎症出现的影响。这些问题从不同的方法学角度出发，包括生理学、生物化学、结构和细胞生物学、药理学、光遗传学和纳米成像技术。重要的是，无脊椎动物和脊椎动物模型的优势将被用来努力将黏附-GPC信号的分子步骤与这些不寻常的受体控制的生理过程联系起来。不仅在方法上，而且特别是在概念层面上，致力于将项目相互关联起来，以促进提取粘附性-GPCR信号的一般原则。

Adhesion-type G protein-coupled receptors form a large class ofseven-transmembrane spanning (7TM) receptors. 7TM receptorshave proven the linchpin for countless physiological functions and atreasure trove for modern pharmaceutical intervention. Adhesion-GPCR appear in stark contrast to the rest of the 7TM receptorsuperfamily as they are by far the most poorly understood 7TMreceptor class. The scientific aims of the Research Unit focus onseveral fundamental aspects of adhesion GPCR biology pertaining tothe physiological and pharmacological features of their signaling.These include their role of mechanosensors, the presence of tetheredagonism as the signal transducing step upon their activation, theanalysis of non-canonical signals controlled through adhesion GPCRsand their effect on cytoskeletal dynamics. In addition, the ResearchUnit strives to deconstruct the impact of adhesion GPCRs on theemergence of neoplasias and inflammation. These questions aretargeted from different methodological angles encompassingphysiology, biochemistry, structural and cell biology, pharmacology,optogenetics and nanoscopic imaging techniques. Importantly, thestrengths of invertebrate and vertebrate models will be used tosynergise efforts in linking molecular steps in adhesion-GPCRsignalling to physiological processes governed by these unusualreceptors. Specific care is dedicated to interlock the projects not onlymethodologically, but especially at the conceptual level to facilitate theextraction of general principles of adhesion-GPCR signalling.