The Molecular basis for action of allosteric ligands in chemokine receptors

趋化因子受体变构配体作用的分子基础

• 批准号: 2284171
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2284171
• 关键词: Molecular; basis; action; allosteric; ligands

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.

G蛋白偶联受体（GPCR）是一个重要的膜受体大家族，当被激素激活时，其激活细胞反应。趋化因子受体参与炎症、病毒感染、愈合和癌症的过程。最近，一类新的变构配体，调节受体的反应，其天然配体，已开发的趋化因子受体。博士项目将侧重于了解变构配体活性的分子基础，因为这对开发新型变构配体非常有利。所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，再加上新的最先进的信号传导测定。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。该项目将提供一个很好的机会，发展结构药理学的技能。该学生将被嵌入在欧洲领先的GPCR研究中心之一的COMPARE。COMPARE由31个研究小组组成，他们拥有不同的专业知识，从药物化学，信号和药理学，先进的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，专注于GPCR，一流的设施，以及超过40名博士生和博士后的充满活力的国际研究环境。