Advancing 'omics analysis with a Sciex ZenoToF 7600 mass spectrometer

理解生物学的复杂性，以及为了我们的利益而进行工程生物学，需要以高准确度和精确度分析广泛的生物分子。质谱学是为数不多的能够洞察这种生物复杂性的技术之一，我们可以用质谱学产生的数据来增加我们对生物系统如何工作的理解。然而，生物学中重要的分子的范围令人困惑。它们可以非常小，例如细胞内葡萄糖转化为能量所涉及的代谢物，也可以非常大，例如催化化学反应的酶，这些化学反应形成所有其他生物分子。它们也可以非常稳定，例如为我们体内的细胞或组成脂肪的一些成分提供支持的胶原蛋白，或者非常脆弱，例如添加到蛋白质中以控制其活性或在细胞中定位的许多结构。该项目旨在提供新一代质谱仪，使我们能够执行所需的复杂分析，以自信地识别复杂生物样本中存在的许多分子的结构，并测量其数量。这是基于对质谱仪中分子裂解方式的改进，以提供关于其结构的信息，使仅在结构上略有不同的分子之间能够区分，并提供准确的定量。该设备是第一台商用飞行时间质谱仪，具有电子激活解离(EAD)，这是一种非常快速的分子裂解方法，因此比其他方法提供了更多的结构信息，并能够改变这种裂解的能量。低能EAD对于具有不稳定化学基团的分子特别有价值，因为裂解的速度确保了不仅仅是这些分子被看到，而高能EAD允许非常稳定的分子的裂解。它还具有改进，允许同时灵敏地测量小片段到大片段，这对于大生物分子和快速准确地定量复杂混合物中的特定分子至关重要。该仪器将为曼彻斯特大学(UOM)在国家重要战略领域的许多研究项目提供好处，并与一些主要的制药和生物技术公司合作。这包括在生物技术方面进行大量研究，例如在生物燃料生产和生物原料利用方面，以及在为可持续化学生产开发清洁生物催化剂方面。它还有利于促进健康的生物科学，例如，有助于了解帕金森氏病中脂肪和脂类的利用如何变化以及炎症如何对生物分子产生不利影响；以及有利于生物科学的可持续农业和食品，例如，有助于识别和了解食品加工过程中产生的食源性过敏原。新仪器将产生世界级的基础生物科学，例如在开发分析技术和方法方面，以更好地了解酶的工作方式和生物系统的功能，以及设计生物过程以利用微生物制造新的化学品。

Understanding the complexity of biology, and engineering biology for our benefit, requires the analysis of a wide range of biomolecules with high accuracy and precision. Mass spectrometry is one of the few techniques capable of providing an insight into this biological complexity, and the data we can generate with mass spectrometry can be used to increase our understanding of how biological systems work. However, the range of molecules important in biology is bewildering. They can be very small, for example the metabolites involved in the conversion of glucose to energy in the cell, to very large, for example the enzymes that catalyse the chemical reactions that make all the other biomolecules. They can also be very stable, such as the collagen that provides the support for the cells in our body or some of the components that make up fats, or very fragile, such as many of the structures added to proteins to control their activity or localization in the cell.This project is to provide a new generation mass spectrometer that will allow us to perform the complex analysis required to confidently identify the structures of, and measure the amount of many of the molecules that are present in complex biological samples. This is based on improvements in the way that molecules are fragmented in the mass spectrometer to provide information on their structure, enable discrimination between molecules that are only subtly different in structure and provide accurate quantification. The equipment is the first commercial time of flight mass spectrometer that has electron activated dissociation (EAD), a way of fragmenting molecules that is very fast and so gives much more information on structure than other methods, and is able to vary the energy of this fragmentation. Low energy EAD is especially valuable for molecules which have labile chemical groups, as the speed of fragmentation ensures it is not just these that are seen, and high energy EAD allows fragmentation of very stable molecules. It also has improvements that allows small to large fragments to be measured sensitively at the same time, which is critical for large biomolecules and for fast and accurate quantification of specific molecules in complex mixtures.This instrument will provide benefit to many research programs at the University of Manchester (UoM) in important strategic areas for the country, and in collaboration with a number of major pharmaceutical and biotechnology companies. This includes substantial research in biotechnology, for example in biofuels production and bio-feedstock utilization, and in the development of clean biological catalysts for sustainable chemical production. It also benefits bioscience for health, for example in understanding how the utilization of fats and lipids changes in Parkinson's disease and how inflammation adversely affects biomolecules, and bioscience for sustainable agriculture and food, for example in identifying and understanding the generation of food-based allergens during food processing. The new instrument will generate world-class and underpinning bioscience, for example in the development of analytical technologies and methodologies to understand better the way enzymes work and how biological systems function, and engineering biological processes to use microorganisms to make new chemicals.