LIPID MAPS

脂质在细胞功能和疾病中起着核心作用。脂质参与细胞功能的范围直到最近才被认识到远远超出其在能量代谢和膜结构中的既定作用。脂质是一组广泛的小的两亲分子，由1,000种不同的分子种类组成，具有许多相似的化学和物理性质。处理脂质的代谢途径是复杂和交织的。开发能够表征脂质代谢物的全球变化的综合代谢组学系统（“脂质组学”）是一项艰巨的任务，但鉴于基因组学、转录组学和蛋白质组学的全球方法所产生的显著回报，这一任务是重要的。我们的联盟已经开发了一种脂质代谢和途径策略，称为脂质地图，适用于脂质组学研究的综合方法。LIPID MAPS的一个目标是采用我们开发的技术来测量受到不同扰动的原代和永生化小鼠巨噬细胞的脂质体，以促进我们对生化途径和脂质代谢调节的机械理解。另一个目标是对小鼠细胞和组织进行脂质组学分析，以提供对不同脂质途径在已建立的疾病模型中在正常和病理条件下如何相互作用的新理解。通过继续在每个联盟实验室中采用一套严格维护的通用生物，生化和分析技术，并通过使用广泛的信息学基础设施，我们将能够整合和分析在更新期间将由这个大规模合作项目产生的广泛数据。我们计划生成“代谢组学网络和路线图”，以定义细胞中所有脂质成分在生物合成、降解和信号传导过程中如何相互作用。所有这些信息将与整个研究界共享，并应作为代谢组学研究和系统生物学整合的范例。脂质图谱也将有助于药物开发，因为脂质在许多疾病中起着关键作用，特别是炎症过程和动脉粥样硬化和糖尿病的代谢综合征。

Lipids play a central role in cellular function and disease. The scope of lipid involvement in cellular function has only recently been recognized to extend well beyond its established roles in energy metabolism and membrane structure. Lipids are an extensive group of small, amphipathic molecules comprised of 1,000's of distinct molecular species possessing many similar chemical and physical properties. The metabolic pathways that deal with lipids are complex and intertwined. Developing an integrated metabolomic system capable of characterizing the global changes in lipid metabolites ("lipidomics") is a daunting task but one that it is important to undertake in light of the significant returns produced by the global approaches of genomics, transcriptomics and proteomics. Our consortium has developed a Lipid Metabolites and Pathways Strategy, termed LIPID MAPS that applies an integrated approach to the study of lipidomics. One goal of LIPID MAPS for the renewal grant period is to employ the technology that we have developed to measure the lipidomes of primary and immortalized mouse macrophages subjected to different perturbations to advance our mechanistic understanding of biochemical pathways and the regulation of lipid metabolism. Another goal is to conduct lipidomic analyses of mouse cells and tissues to provide new understanding of how different lipid pathways interact under normal and pathological conditions in established models of disease. By continuing to employ a rigorously maintained set of common biological, biochemical, and analytical technologies in each of the consortium laboratories, and by using an extensive informatics infrastructure, we will be able to integrate and analyze the extensive data that will be generated by this large scale collaborative project during the renewal period. We plan to generate "metabolomic networks and roadmaps" that will define how all of the lipid components of a cell interact during biosynthesis, degradation, and signaling. All of this information will be shared with the entire research community and should serve as a paradigm for metabolomics research and systems biology integration. LIPID MAPS will also contribute to drug development since lipids play critical roles in numerous diseases, especially inflammatory processes and the metabolic syndrome underlying atherosclerosis and diabetes.