GlasBioPhys: an integrated facility for the analysis of biomolecular interactions

GlasBioPhys：用于分析生物分子相互作用的综合设施

• 批准号: BB/T018062/1
• 负责人: Glenn Burley
• 金额: $ 32.8万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT018062%2F1
• 关键词: GlasBioPhys; integrated; facility; analysis; biomolecular

Understanding the structure and functions of biomolecules is essential if we are exploit them for medical and industrial applications. Biomolecules such as proteins, drugs, DNA and RNA all rely on a series of weak (non-covalent) bonds, which work in concert to form specific molecular complexes. These non-covalent interactions are key to all biological processes such as how genes are switched on by proteins, how enzymes function, how molecular machines assemble inside cells and how drugs work. Our understanding of this requires the use of a range of complex equipment, often requiring several pieces of equipment to fully characterize a biomolecule, such as Surface Plasmon Resonance to measure how much affinity biomolecules have for each other or the rates at which they bind to each other. We often use a technique called Isothermal Titration Calorimetry to determine the thermodynamics of interaction and fluorescence polarization spectroscopy to report on how proteins change their conformation when they interact with a partner. These instruments all measure biomolecule interactions in isolation, they are low-throughput and require the development and isolation of experimental conditions for each technique. This application proposes to establish a UK wide facility to measure all of these interactions within a single instrument (switchSENSE heliX, launched in October 2019). At present, there is no existing infrastructure which can match the capabilities of the SwitchSENSE heliX instrument currently on the market. We proposed to use this to support established BBSRC funded academic researchers and industrial partners in Glasgow and more widely in the UK. These researchers will use the SwitchSENSE helix to investigate DNA-binding interactions with drugs, DNA and RNA-binding and how this affects gene expression, post-translational modification of proteins and protein-protein interactions all possible in a streamlined high-throughput fashion. In addition, this grant will facilitate the training of researchers, supporting the training of doctoral students and also access to the equipment by industry to help build the UK capability and sustainability in the area of biomolecular interactions.

了解生物分子的结构和功能是必不可少的，如果我们利用它们的医疗和工业应用。生物分子如蛋白质、药物、DNA和RNA都依赖于一系列弱（非共价）键，这些键协同作用形成特定的分子复合物。这些非共价相互作用是所有生物过程的关键，例如基因如何被蛋白质打开，酶如何发挥作用，分子机器如何在细胞内组装以及药物如何起作用。我们对这一点的理解需要使用一系列复杂的设备，通常需要几件设备来完全表征生物分子，例如表面等离子体共振来测量生物分子彼此之间的亲和力或它们彼此结合的速率。我们经常使用一种称为等温滴定量热法的技术来确定相互作用的热力学，并使用荧光偏振光谱来报告蛋白质在与伴侣相互作用时如何改变其构象。这些仪器都是孤立地测量生物分子相互作用，它们是低通量的，并且需要为每种技术开发和分离实验条件。该申请建议建立一个英国范围的设施，以在单个仪器（switchSENSE heliX，于2019年10月推出）中测量所有这些相互作用。目前，没有任何现有的基础设施可以匹配目前市场上的SwitchSENSE heliX仪器的功能。我们建议利用这一点来支持建立BBSRC资助的学术研究人员和工业合作伙伴在格拉斯哥和更广泛的英国。这些研究人员将使用SwitchSENSE螺旋来研究DNA与药物、DNA和RNA结合的相互作用，以及这如何影响基因表达、蛋白质的翻译后修饰和蛋白质-蛋白质相互作用，所有这些都可能以流线型的高通量方式进行。此外，这笔赠款将促进研究人员的培训，支持博士生的培训，并通过行业获得设备，以帮助建立英国在生物分子相互作用领域的能力和可持续性。