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

脂质代谢改变是大多数人类疾病的共同特征，包括心血管、癌症、炎症、痴呆和自身免疫。因此，组织和细胞中脂质的准确定量和鉴定可以提供对病理学潜在机制的重要见解。对人类疾病重要的脂质类别的实例包括氧脂类，其包含在炎症期间由酶产生的结构上不同的类二十烷酸和类胡萝卜素，以及鞘脂和神经酰胺，越来越多地认识到在癌症和器官和组织发育中发挥关键作用的脂质。脂质占所有已知代谢物的三分之一，其灵敏和特异性测量是世界各地不断增长的研究需求的主要领域，无论是生物医学研究还是许多工业应用。作为证据，Wellcome Trust资助的资源LIPID MAPS（我们在卡迪夫托管）支持约65K研究人员的全球用户群。准确和灵敏的脂质定量分析需要一种称为质谱的生物物理方法。这种方法基于分子量和电荷测量分子。这通常在色谱法之前进行，该方法首先基于脂质的物理性质在其质量检测之前分离脂质。脂质的质谱被称为脂质组学，随着人们对脂质对人类疾病的重要性的日益认识，英国和全球研究界越来越需要提供脂质组学。由于其专业性质，lipidomics MS通常通过访问在采购设备以及所需的高水平技术支持方面投入了大量时间和精力的设施来提供。在卡迪夫，奥唐纳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在奥唐纳集团工作超过13年，包括担任设施经理。我们的设施自2005年以来一直在运行，拥有三台仪器，全天候分析样品。然而，随着老化的QTrap现在退役，我们有可能失去总分析能力的三分之一。这将严重影响我们支持自己和合作者研究的能力。该卡迪夫设施支持本地研究在我们自己的组，其他卡迪夫为基础的研究人员，并在英国和国际上正在进行的外部工作相结合。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职权范围的相关性。我们的仪器可供所有需要脂质组学的人使用，我们根据用户的需求运营成本回收和协作模式。用7500QTrap取代老化的4000QTrap将为我们自己的研究能力提供巨大的好处，但重要的是，我们支持内部和外部合作研究的能力，正如我们的支持案例所述。近年来，人们对脂质组学的兴趣激增，对我们专业知识的需求呈指数级增长。这种新仪器不仅可以推进我们自己的研究，还可以让我们有能力通过最新和最高通量的检测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.