The Molecular basis for action of allosteric ligands in chemokine receptors

G蛋白偶联受体（gpcr）是一个重要的膜受体家族，当被激素激活时可激活细胞反应。趋化因子受体参与炎症、病毒感染、愈合和癌症的过程。最近，一类调节受体对其天然配体反应的新型变构配体已被开发用于趋化因子受体。博士项目将重点研究变构配体活性的分子基础，这对开发新的变构配体是非常有利的。使用的主要技术之一将是先进的蛋白质工程和高通量扫描诱变，再加上最新的信号分析。对于数据的解释，候选人还将使用结构生物信息学和机器学习技术。该项目将提供一个极好的机会来发展结构药理学的技能。该学生将被嵌入COMPARE，这是欧洲GPCR研究的主要中心之一。COMPARE由31个具有不同专业知识的研究小组组成，从药物化学、信号和药理学、高级光学显微镜到结构生物学、生理学和机器学习。这是一个非常独特的专业知识的集合，专注于gpcr，优秀的设施，以及一个充满活力的国际研究环境，超过40名博士生和博士后。

G protein coupled receptors (GPCRs) are a large pharmacologically important family of membrane receptors that activate a cellular response when activated by a hormone. The chemokine receptors are involved in processes of inflammation, viral infections, healing and cancer. Recently, a novel class of allosteric ligands that modulate the receptor response to its native ligand, has been developed for chemokine receptors. The PhD project will focus of understanding the molecular basis for the allosteric ligand activity, as it would be very advantageous for the development of novel allosteric ligands. One of the main techniques used will be advanced protein engineering and high throughput scanning mutagenesis coupled with novel state of the art signalling assays. For the interpretation of data, the candidate will also use structural bioinformatics and machine learning techniques. The project will provide an excellent opportunity to develop skills in structural pharmacology. The student will be embedded in COMPARE, one of the leading centres for GPCR research in Europe. COMPARE consists of 31 research groups with diverse expertise ranging from medicinal chemistry, signalling and pharmacology, advanced optical microscopy to structural biology, physiology and machine learning. It is quite a unique constellation of expertise focused on GPCRs, excellent facilities, and a vibrant international research environment of over 40 PhD students and postdocs.