BEACON - A multi-user and multi-project facility for biological macromolecules and nanoparticles characterization in solution

生物实体由小分子(如水)、大分子(蛋白质、核酸、脂类、多糖)、超分子组件或大分子复合体组成，它们组装成亚细胞细胞器和细胞，进而形成组织和器官等超细胞系统。生物系统的关键特征之一是复杂的、特定的或非特定的、分子内和分子间的相互作用，它决定了结构，并进一步决定了与结构相关的生物功能。例如，血红蛋白是一种四聚体蛋白质，每单位结合和运输四个氧分子，然后将它们释放到肌红蛋白。生物分子之间的接触，或生物分子之间的相互作用，也是病原体入侵和各种疾病的原因。SARS-CoV-2病毒通过其刺突蛋白的受体结合域与宿主靶细胞受体ACE2结合。神经退行性疾病，如阿尔茨海默氏症或帕金森氏症，与有毒蛋白质的Pron样繁殖和聚集有关。能够测量生物大分子和纳米粒子在溶液中的关键物理参数(例如，质量、大小、形状、相互作用和共轭)将回答生物学中的许多基本问题，并帮助我们理解生命规律。这些答案和规则不仅将有助于推进生物技术和生物科学，还将指导我们解决人类面临的重大挑战(例如，新的和重新出现的疾病、流行病、气候变化和可持续性等)。这项提议的目的是购买一种最先进的设备，以实现生物物理测量。这些设备将支持一系列支持BBSRC优先事项的研究项目，这些项目与谢菲尔德大学四个旗舰研究所(健康寿命、神经科学、能源和可持续食品)的愿景完全一致。最重要的是，该设备使大学新冠肺炎反应小组能够衡量和量化大学生产的生物试剂的质量，以支持冠状病毒的诊断测试。该设备还增强了我们对当前和未来紧急情况的反应和准备。这些设备将由大学化学和生物工程系的一个专门团队进行维护。

Biological entities are composed of small molecules (e.g., water), macromolecules (proteins, nucleic acids, lipids, polysaccharides), supramolecular assemblies or macromolecular complexes, which assemble into subcellular organelles and cells, which in turn form supracellular systems such as tissues and organs. One of the key features of biological systems is the complex, specific or non-specific, intra- and inter-molecular interactions, which determine the structure and, further, the biological functions associated with the structure. As an example, hemoglobin is a tetrameric protein that binds and transports four oxygen molecules per unit and then releases them to myoglobin. The contacts between biological molecules, or biomolecular interactions, are also responsible for pathogen invasion and various diseases. SARS-CoV-2 virus binds to ACE2, the host target cell receptor, through the receptor binding domain of its spike protein. Neurodegenerative diseases such as Alzheimer's or Parkinson's are associated with the prion-like propagation and aggregation of toxic proteins. The ability to measure key physical parameters (e.g., mass, size, shape, interaction, and conjugation) of biological macromolecules and nanoparticles in solution will answer many FUNDAMENTAL QUESTIONS IN BIOLOGY and help us to understand THE RULES OF LIFE. Not only will the answers and the rules help to advance biotechnology and biological science, they guide our solutions to the grand challenges facing humanity (e.g., new and re-emerging diseases, epidemic, climate change, and sustainability etc). The aim of this proposal is to purchase a state-of-the-art equipment to enable biophysical measurements. The equipment will support a host of research projects underpinning BBSRC priorities, which neatly align with the visions of the four flagship institutes at the University of Sheffield (Healthy Lifespan, Neuroscience, Energy, and Sustainable Food). On top of that, the equipment allows the University COVID-19 response team to measure the quality of and quantify the biological reagents manufactured at the University to support diagnostic testing of coronavirus. The equipment also enhances our response and preparedness for current and future emergency. This equipment will be maintained by a dedicated team in the Department of Chemical & Biological Engineering at the University.