A mass spectrometry centre for the analysis of glycerolipids, glycerophospholipids and sphingolipids, and their lipid oxidation products

脂类是构成细胞周围细胞膜的脂肪分子；没有它们，生命就不会存在。然而，这只是脂质在生物学中扮演的重要角色之一。例如，脂质还参与细胞内和细胞之间的多种形式的通讯，细胞膜的脂组成影响嵌入其中的蛋白质的活性，例如那些将分子输送进和运出细胞的蛋白质。与食用油腐烂一样，与氧气反应对脂质的损害与它们在疾病中的许多作用有关。因此，分析血脂并了解它们在生物学中的作用是非常重要的研究领域。然而，对脂质的全面分析是具有挑战性的，因为它们是一组非常复杂的分子，在人类细胞中有超过10万种不同的类型，如果包括细菌和其他微生物，还会有更多。它们中的许多具有非常相似的化学结构，因此很难区分它们，但作用却非常不同，因此正确识别它们是很重要的。我们将用这笔赠款购买的设备具有基于分子形状的额外维度来分离分子，这将大大增加我们能够区分的不同脂质的数量，并将使广泛的研究能够帮助理解它们在生物学中的复杂作用。关于血脂在生活中的重要性，有很多例子。例如，它们在控制细胞生长到细胞死亡方面发挥作用，包括在炎症等条件下特别重要的过程。脂类还会影响细胞中蛋白质的活性，特别是细胞膜中的蛋白质，其中许多蛋白质是吗啡和胰岛素等药物的靶标。分析与膜蛋白相关的脂类，以及这些脂类的变化对蛋白质活性的影响，对于理解这些影响以及它们可能随着年龄或饮食的变化而变化，或在其他不同的领域，如生物燃料的生产或细菌复制过程中可能成为抗微生物药物的新靶点，具有重要意义。脂类含有许多可被活性化学物质攻击的部位，这些受损的脂类本身可能具有生物活性，或者与其他分子反应，从而影响其功能。低密度脂蛋白，或坏胆固醇就是一个例子。低密度脂蛋白中脂质的氧化损伤被认为是导致心脏病发作和中风的变化的原因。我们需要能够分析在这些反应中产生的不同脂质，它们如何与生物系统相互作用或反应，以及这对生物系统有什么影响。这项赠款提案将提供仪器，使我们能够进行所需的复杂分析，以自信地识别和测量复杂生物样本中存在的脂类的数量。将使用的主要技术是质谱学，它非常准确地测量分子的重量，并能够分解分子以获得关于其结构的信息。然而，目前的方法并不总是能够分离复杂混合物中的所有单独成分，以便对其进行全面分析，特别是对影响细胞行为的低丰度分子。新仪器将提供额外的能力，通过一个额外的维度来分离分子，称为离子迁移率，它能够根据分子的形状分离分子。该设备将是第一个可用的新设计的仪器，允许更精细的分子分离(它有一个循环离子迁移池，提供更长的有效分离路径长度)。这将使我们能够更准确地测量存在的脂质以及它们变化的方式，从而在许多重要领域更好地理解生物学。

Lipids are the fatty molecules that make up the membranes that surround cells; without them life would not exist. However, this is only one of the important roles that lipids play in biology. For example, lipids are also involved in many forms of communication within and between cells, and the lipid composition of the cell membrane affects the activity of proteins embedded in it, such as those that transport molecules in and out of the cell. Damage to lipids by reaction with oxygen, in the same way that cooking oils go rancid, is related to many of their roles in disease. Hence, the analysis of lipids and understanding their roles in biology are very important areas of research. However, the comprehensive analysis of lipids is challenging as they are a very complex set of molecules, with over 100,000 different types in human cells, and many more when bacteria and other microorganisms are included. Many of them have very similar chemical structures, making it hard to tell them apart, but very diverse effects, so it is important to identify them correctly. The equipment we will buy with this grant has an extra dimension for the separation of molecules, based on their shape, which will greatly enhance the number of different lipids that we are able to distinguish and will enable a wide range of research to help understand their complex roles in biology. There are many examples of how lipids are important in life. For example, they play a role in controlling cell growth to cell death, including processes particularly important in conditions such as inflammation. Lipids can also affect the activity of proteins in the cell, and particularly those in the cell membranes, many of which are targets for drugs such as morphine and insulin. Analysis of the lipids associated with membrane proteins, and the effects that changing of these lipids has on the activity of the proteins, is important in understanding these effects and how they may change with age or diet, or in other diverse areas, such as the production of biofuels or processes in bacterial replication that could be new targets for antimicrobials. Lipids contain many sites that can be attacked by reactive chemical species, and these damaged lipids can themselves have biological activity or react with other molecules impairing their function. An example is LDL, or bad cholesterol. Oxidative damage to the lipids in LDL is thought to be responsible for changes that lead to heart attacks and strokes. We need to be able to analyse the different lipids that are generated in these reactions, how they interact with or react with biological systems, and what effects this has on the biological system. This grant proposal is provide instrumentation that will allow us to perform the complex analysis required to confidently identify and measure the amount of lipids that are present in complex biological samples. The main technique to be used is mass spectrometry, which measures the weight of molecules very accurately, as well as being able to break up the molecules to get information on their structure. However, the current methods are not always able to separate all the individual components in complex mixtures to allow their full analysis, especially of low abundance molecules that affect cell behaviour. The new instrument will provide extra capabilities through an additional dimension for separation of the molecules, called ion mobility, which is able to separate molecule based on their shape. The equipment will be the first available of a new design of instrument that allows much finer separation of molecules (it has a cyclic ion mobility cell providing much longer effective separation path lengths). This will allow us to do more accurate measurement of the lipids present and the way in which they are changed, leading to a much better understanding of biology in many important areas.