GlasBioPhys: an integrated facility for the analysis of biomolecular interactions

如果我们要将生物分子用于医疗和工业应用，了解生物分子的结构和功能是必不可少的。蛋白质、药物、DNA和RNA等生物分子都依赖于一系列弱的(非共价)键，这些键协同工作形成特定的分子复合体。这些非共价相互作用是所有生物过程的关键，例如蛋白质如何启动基因，酶如何发挥作用，分子机器如何在细胞内组装，以及药物如何发挥作用。我们对此的理解需要使用一系列复杂的设备，通常需要几台设备来充分表征生物分子，例如表面等离子体共振，以测量生物分子之间有多少亲和力或它们相互结合的速率。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，需要为每种技术开发和隔离实验条件。这项申请建议建立一个英国范围的设施，在单一仪器(SwitchSENSE Helix，于2019年10月推出)中测量所有这些相互作用。目前，没有现有的基础设施可以与目前市场上的SwitchSENSE螺旋仪器的功能相匹配。我们建议用这笔钱来支持在格拉斯哥和更广泛的英国由BBSRC资助的现有学术研究人员和工业合作伙伴。这些研究人员将使用SwitchSENSE螺旋来研究与药物的DNA结合作用、DNA和RNA结合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--所有这些都可能以简化的高通量方式实现。此外，这笔赠款将促进研究人员的培训，支持博士生的培训，并按行业获得设备，以帮助英国在生物分子相互作用领域建立能力和可持续性。

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.