New high resolution mass spectrometry facilities for macromolecules and metabolites at the University of East Anglia

东安格利亚大学新的大分子和代谢物高分辨率质谱设备

• 批准号: BB/T017708/1
• 负责人: Nicolas Le Brun
• 金额: $ 62.44万
• 依托单位: University of East Anglia
• 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%2FT017708%2F1
• 关键词: New; resolution; mass; spectrometry; facilities

Mass spectrometry has revolutionized many aspects of research in the molecular sciences, through its ability to unambiguously identify molecules by measuring their mass with incredible accuracy. UEA researchers have pioneered the use of a particular type of mass spectrometry in studies of proteins, fascinating workhorse molecules of life that are dynamic in the way they interact with each other and with small molecules. Many proteins contain fragile metal cofactors that are able to react chemically in ways that proteins alone cannot. These cofactors are often pre-assembled (by complex pathways) and then inserted into the protein much like a factory assembly line. The chemistry that goes on at these cofactors often involves changes in mass that controls protein function. UEA researchers have used a type of gentle mass spectrometry that preserves the fragile cofactors, and have been able to 'watch' reactions happen by measuring the resulting usually small changes in mass, providing unprecedented insight into processes that are essentially invisible to other methods. This work has revealed how bacteria sense key environmental ques such as oxygen and iron availability, which are known to be virulence factors that regulate infection. The aim of this bid for a new mass spectrometer with state of the art capabilities is to apply mass spectrometry to a broader range of cofactor-containing proteins that cannot be studied using existing limited facilities. Proposed projects include understanding the assembly of the hydrogenase cofactor and the development of biohybrid materials, both of which are relevant to bioenergy, small molecules that bind DNA as tools and potential therapeutics, and the discovery of novel natural antifungal molecules that may have potential for use in the protection of valuable crops. The new instrument will benefit researchers at UEA more broadly as it will make accessible technologies that are not currently available.

质谱仪通过以令人难以置信的准确度测量分子质量来明确识别分子的能力，彻底改变了分子科学研究的许多方面。UEA的研究人员开创了一种特殊类型的质谱法在蛋白质研究中的应用，蛋白质是生命中迷人的主力分子，它们彼此之间以及与小分子之间的相互作用是动态的。许多蛋白质含有脆弱的金属辅因子，它们能够以蛋白质本身无法进行的方式进行化学反应。这些辅因子通常是预先组装的（通过复杂的途径），然后像工厂装配线一样插入蛋白质中。在这些辅因子上发生的化学反应通常涉及控制蛋白质功能的质量变化。UEA的研究人员使用了一种温和的质谱法，可以保留脆弱的辅因子，并且能够通过测量产生的通常很小的质量变化来“观察”反应的发生，为其他方法基本上不可见的过程提供了前所未有的洞察力。这项工作揭示了细菌如何感知关键的环境问题，如氧气和铁的可用性，这是已知的调节感染的毒力因子。此次招标的目的是将具有最先进能力的新质谱仪应用于更广泛的含辅因子的蛋白质，这些蛋白质无法使用现有的有限设施进行研究。拟议的项目包括了解氢化酶辅因子的组装和生物杂交材料的开发，这两者都与生物能源，结合DNA作为工具和潜在治疗剂的小分子有关，以及发现可能有潜力用于保护有价值作物的新型天然抗真菌分子。新仪器将使东英吉利大学的研究人员更广泛地受益，因为它将使目前无法获得的技术变得可访问。