Funding for a QTrap Mass spectrometer for the Cardiff Lipidomic Group.

脂代谢异常是大多数人类疾病的共同特征，包括心血管疾病、癌症、炎症、痴呆症和自身免疫。因此，准确地定量和识别组织和细胞中的脂类可以为深入了解潜在的病理机制提供重要的帮助。对人类疾病很重要的脂类的例子包括氧化脂，它由炎症过程中酶产生的结构多样化的二十烷基类和前列腺素组成，以及神经鞘脂脂和神经酰胺，这两种脂类越来越被认识到在癌症和器官和组织发育中发挥关键作用。脂质占所有已知代谢物的三分之一，其灵敏和特异的测量是世界各地日益增长的研究需求的一个主要领域，无论是生物医学研究，还是许多工业应用。作为这一点的证据，惠康信托资助的资源脂质地图(我们在加的夫托管)支持大约65K名研究人员的全球用户基础。准确和灵敏的脂类定量分析需要一种称为质谱学的生物物理方法。这种方法根据分子的相对分子质量和电荷来测量分子。这之前通常是层析，这是一种在质量检测之前首先根据脂类的物理性质分离脂类的方法。脂类的质谱学被称为脂类组学，随着人们对脂类对人类疾病重要性的日益认识，在英国和全球研究界提供脂类组学的需求越来越大。由于其专业性，通常通过获得在采购设备以及所需的高水平技术支持方面投入大量时间和精力的设施来提供。在加的夫，O‘Donnell在脂质生物化学方面有大约30年的经验，自1997年以来一直使用MS进行脂质结构研究，而Tyrrell在O’Donnell集团工作了13年，包括担任设施经理。我们的设施自2005年以来一直在运营，拥有三台全天候分析样品的仪器。然而，随着老化的QTrap现在即将退役，我们可能会失去三分之一的总分析能力。这将严重影响我们支持自己和合作者的研究的能力。加的夫的设施支持我们自己团队中的本地研究、其他加的夫的研究人员以及在英国和国际上正在进行的外部工作的组合。下面，我们列出了我们目前的合作者，证明了我们研究的广度及其与MRC任务的相关性。我们的仪器向所有需要脂质组学的人提供，我们根据用户的需求运营成本回收和协作模式。用7500QTrap替换老化的4000QTrap将为我们自己的研究能力提供巨大的好处，但重要的是，我们能够支持内部和外部的协作研究，正如我们的支持案例中概述的那样。近年来，人们对脂质组学的兴趣呈爆炸式增长，对我们专业知识的需求也呈指数级增长。这一新仪器将使我们不仅能够推进我们自己的研究，还将使我们有能力通过可用的最新和最高吞吐量的分析方法支持更多的英国和国际合作。

Altered lipid metabolism is a common feature of most human diseases, including cardiovascular, cancer, inflammation, dementia and autoimmunity. Thus, accurate quantitation and identification of lipids in tissues and cells can provide significant insight into underlying mechanisms of pathology. Examples of lipid categories that are important for human disease include oxylipins, which comprise structurally diverse eicosanoids and prostaglandins generated by enzymes during inflammation, as well as sphingolipids and ceramides, lipids which are increasingly recognized to play key roles in cancer and organ and tissue development. Lipids make up a third of all known metabolites, and their sensitive and specific measurement is a major area of growing research need across the world, both for biomedical research but also many industrial applications. As evidence of this, the Wellcome Trust-funded resource LIPID MAPS (which we host at Cardiff) supports a global user base of around 65K researchers. Accurate and sensitive quantitative analysis of lipids requires a biophysical method called mass spectrometry. This approach measures molecules based on their molecular weight and charge. This is most often preceded by chromatography, a method which first separates the lipids based on their physical properties in advance of their mass detection. Mass spectrometry of lipids is termed lipidomics, and with the growing appreciation of the importance of lipids to human disease, there is increasing need for provision of lipidomics across the UK and global research community. Due to its specialist nature, lipidomics MS is generally provided through access to facilities which have invested significant time and effort in both procuring equipment as well as the high level of technical support required. At Cardiff, O'Donnell has around 30 yrs experience in lipid biochemistry and has used MS for lipid structural studies since 1997, while Tyrrell has been based in the O'Donnell group for >13 yrs, including working as Facilities Manager. Our facility has been operational since 2005, hosting three instruments which analyse samples around the clock. However as the ageing QTrap is now being decommissioned, we risk losing a third of our total analytical capacity. This will critically impact our ability to support both our own research and that of our collaborators. The Cardiff facility supports a combination of local research in our own group, other Cardiff-based researchers, and external work being conducted both in the UK and internationally. Below, we list our current collaborators, evidencing the breadth of our research and its relevance to MRC remit. Our instruments are available to all who have need for lipidomics, and we operate both cost-recovery and collaborative models depending on users' needs. Replacing the ageing 4000QTrap with the 7500QTrap would provide enormous benefits for our own research capacity, but importantly, our ability to support collaborative research internally and externally, as outlined in our case for support. Interest in lipidomics has exploded in recent years, and the demand on our expertise has grown exponentially. This new instrument will allow us to not only advance our own research but also give us the capacity to support more UK and international collaborations with the newest and highest throughput assays available.