Oxidative Lipidomics Core

由于对ARDS的发病机制认识不足，目前尚无有效的药物治疗。P01的首要重点是肺对一种新的肺毒素和调节剂的反应机制，这种毒素和调节剂是一种阴离子磷脂，即心磷脂（CL），来源于急性肺损伤期间受损宿主细胞的细菌或线粒体。因此，阐明CL的不同分子种类、其代谢物及其与其他肺脂质及其过氧化产物的相互作用的新代谢和生化途径是P01的所有四个项目的基础。氧化脂质组学核心（Core B）旨在让项目中的研究人员对Cls的所有主要分子种类、其他不同类别的脂质及其氧化产物进行详细分析-识别、表征和成像。这将通过使用基于不同版本的质谱（MS）结合液相色谱（LC）或高效薄层色谱（HPTLC）方案的先进技术来实现。氧化脂质组学核心B的具体目的是：1.在设计和实施实验时提供专业知识，使用适当的技术来识别，表征和定量脂质，特别是Cls。制备并优化分析样品，以检测脂质和氧化脂质的单个分子种类。2.为肺组织中不同类型的单个分子种类和氧化脂质的质谱成像提供机会。3.评估实验结果并提出后续实验方向。4.提供P01项目中用于评估脂质组学/氧化脂质组学生物标志物的任何仪器和技术的使用和访问培训。通过协助项目的分析工作，核心将促进CL作为急性肺损伤新分子信号的机制研究，从而有助于开发新的治疗模式。

Currently, there is no effective pharmacologic therapy against ARDS because of insufficient knowledge of the pathogenesis mechanisms. The overarching focus of the P01 is on mechanisms of pulmonary responses to a new pulmonary toxin and regulator, the anionic phosholipid, cardiolipin (CL) originating from bacteria or mitochondria of damaged host cells during acute lung injury. Thus elucidation of novel metabolic and biochemical pathways of different molecular species of CL, its metabolites and their interactions with other pulmonary lipids and their peroxidation products are fundamental to all four projects of the P01. The Oxidative Lipidomics Core (Core B) has been designed to allow researchers in the projects to perform detailed analysis - identification, characterization and imaging - of all major molecular species of Cls, other different classes of lipids as well as their oxidation products. This will be achieved by using sophisticated state-of-the art techniques based on different versions of mass-spectrometry (MS) combined with liquid¿ chromatography (LC) or high-performance thin-layer chromatography (HPTLC) protocols. Specific Aims of the Oxidative Lipidomics Core B are to: 1. Provide professional expertise in the design and implementation of experiments using adequate techniques for identification, characterization, and quantification of lipids, particularly Cls. Prepare and optimally analyze samples to detect individual molecular species of lipids and oxidized lipids. 2. Provide opportunities for mass-spectrometric imaging of different types of individual molecular species and oxidized lipids in lung tissues. 3. Evaluate experimental results and propose subsequent experimental direction. 4. Provide training in the use of and access to any instrumentations and techniques used within the P01 project to assess lipidomics/oxidative lipidomics biomarkers. By assisting the Projects in the analytical work, the Core will facilitate studies of the mechanisms through which CL functions as a new molecular signal in acute lung injury hence contributes to the development of new therapeutic modalities.