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

通过以令人难以置信的精度测量分子的质量，质谱仪能够毫不含糊地识别分子，从而彻底改变了分子科学研究的许多方面。UEA的研究人员率先在蛋白质研究中使用了一种特殊类型的质谱学，蛋白质是生命中令人着迷的主力分子，它们相互作用和与小分子相互作用的方式是动态的。许多蛋白质含有脆弱的金属辅因子，这些辅因子能够以蛋白质本身所不能的方式进行化学反应。这些辅因子通常被预先组装(通过复杂的途径)，然后插入到蛋白质中，就像工厂的装配线一样。在这些辅因子上发生的化学变化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学，它保留了脆弱的辅助因子，并能够通过测量结果通常很小的质量变化来“观察”反应的发生，为其他方法基本上看不到的过程提供了前所未有的洞察。这项工作揭示了细菌如何感知关键的环境问题，如氧气和铁的可获得性，这是已知的调节感染的毒性因素。这次竞标具有最先进能力的新质谱仪的目的是将质谱学应用于更广泛的含有辅因子的蛋白质，这些蛋白质无法使用现有有限的设施进行研究。拟议的项目包括了解氢酶辅助因子的组装和生物杂化材料的开发，这两项都与生物能源、将DNA结合为工具和潜在疗法的小分子有关，以及发现可能在保护有价值的作物方面使用的新型天然抗真菌分子。新仪器将使UEA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用。

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.