SPRINT: A SuPer-Resolution time-resolved ImagiNg and specTroscopy facility for rapid biomolecular analysis

如果我们要将生物分子用于医疗或工业应用，了解生物分子的结构和动力学是必不可少的。蛋白质和酶等分子是动态的，了解它们在细胞途径和生物过程中的相互作用可以为基本机制提供新的见解，并支持新的治疗诊断和药物的开发。我们通常需要使用一系列复杂的设备来充分理解和表征生物分子。可视化分子相互作用的一种常见方法是使用专门的显微镜；然而，这种方法只能解析相距大于250 nm(0.00025毫米)的结构。细胞中发现的蛋白质和其他分子比这要小得多(约0.00001毫米)，因此要分辨单个蛋白质及其相互作用，需要使用更先进的显微镜技术，通常称为“超分辨率”显微镜。该申请计划建立一个苏格兰的显微镜设备，采用超分辨率技术，特别是一种‘量子尺’(称为Flim-FRET，能够测量0.00001毫米范围内发生的分子相互作用)和一种名为FCS的方法，该方法允许在活细胞的微观区域研究单个分子及其行为。使用这一新设施将对苏格兰各地的学术研究人员产生重大影响。该设施还将促进对年轻的早期研究人员进行尖端技术方面的培训。它还将支持博士生的培训，确保下一代科学家拥有所需的技能，以实现重大的新科学突破，帮助建设英国在生物分子相互作用领域的能力和可持续性。

It is essential to understand the structure and dynamics of biomolecules if we are to exploit them for medical or industrial applications. Molecules such as proteins and enzymes are dynamic, and understanding their interactions within cell pathways and biological processes can provide new insight into fundamental mechanisms and support the development of new therapeutic diagnostics and drugs. We usually require the use of a range of complex equipment to understand and characterise biomolecules fully. One common way to visualise molecular interactions is through the use of specialised microscopes; however, this approach can only resolve structures that are greater than 250 nm apart (0.00025 mm). Proteins and other molecules found in cells are much smaller than this (around 0.00001 mm), and therefore to resolve single proteins and their interactions requires access to more advanced microscopy techniques, commonly referred to as "super-resolution" microscopy. This application proposes to establish a Scottish microscopy facility that adopts super-resolution techniques, in particular a 'quantum-ruler' (called FLIM-FRET, capable of measuring molecular interactions happening within 0.00001 mm) and a method called FCS that allows single molecules and their behaviours to be studied in microscopic regions of living cells. Access to this new facility will have a significant impact on academic researchers across Scotland. This facility will also facilitate the training of young early-stage researchers in cutting-edge technology. It will also support the training of doctoral students ensuring the next generation of scientists have the skills required to deliver significant new scientific breakthroughs to help build the UK capability and sustainability in the area of biomolecular interactions.