LIPID MAPS

描述(由申请者提供)：脂质在细胞功能和疾病中起着核心作用。直到最近，人们才认识到脂质参与细胞功能的范围远远超出了它在能量代谢和膜结构中的既定作用。脂类是一组广泛的小的两亲性分子，根据结构及其生物合成来源分为一系列类别。尽管如此，所有这些化合物都具有许多相似的化学和物理性质。由于这些相似之处，处理脂质的代谢途径是复杂和相互交织的。开发一个能够描述全球脂质代谢物变化的综合代谢系统(“脂质组学”)是一项艰巨的任务，但鉴于基因组学和蛋白质组学的全球方法产生的重大回报，必须开展这项工作。我们的联盟开发了一种脂类代谢物和途径策略，称为脂类图谱，它应用了一种全球综合的方法来研究脂类组学。在这一授权期内，脂质图谱的具体目标是开发必要的技术并实施一项综合研究计划，这将使脂质组学成为一个功能齐全的研究领域。通过在每个联盟实验室中使用一套严格维护的通用生物、生化和分析技术，以及通过使用广泛的信息学基础设施，我们将能够集成和分析这个大型合作项目将产生的大量数据。我们将能够生成“路线图”，它将定义细胞的所有脂质成分如何通过复杂的脂体网络从生物合成到移除，包括它们作为第二信使的重要角色。所有这些信息都将与整个研究界共享，并将极大地帮助为其他系统开发代谢组学。此外，脂类图谱还应有助于药物开发，因为脂类在许多疾病中发挥关键作用，包括炎症过程、动脉粥样硬化、阿尔茨海默病、癌症和中风。尽管发展脂类组学领域会产生明显的好处，但目前还没有大规模的国内或国际项目来进行这样的研究。我们相信，建立脂类组学领域的实验技术现在已经到位，脂类图谱是实现这一目标的可行战略。这将导致将脂类整合到21世纪生物学的总体焦点中，即整合到完全定量的系统水平生物学中。

DESCRIPTION (provided by applicant): 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 that are divided into a series of classes based on structure and their biosynthetic origins. Still, all of these compounds possess many similar chemical and physical properties. Because of these similarities, 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 and proteomics. Our consortium has developed a Lipid Metabolites And Pathways Strategy, termed LIPID MAPS that applies a global integrated approach to the study of lipidomics. The specific aim of LIPID MAPS for this grant period is to develop the requisite technology and conduct an integrated research program that will establish lipidomics as a fully functioning research field. By employing 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 large amount of data that will be generated by this large scale collaborative project. We will be able to generate "road maps" that will define how all of the lipid components of a cell move through the complex lipidomic network from biosynthesis to removal, including their important roles as second messengers. All of this information will be shared with the entire research community and should greatly aid in the development of metabolomics for other systems. In addition, LIPID MAPS should also aid in drug development since lipids play critical roles in numerous diseases, including inflammatory processes, atherosclerosis, Alzheimer's disease, cancer and stroke. Despite the clear benefits that developing a lipidomics field would produce, no large scale national or international programs for such a study exist. We believe that the experimental technologies are now in hand for establishing the field of lipidomics and that LIPID MAPS represents a viable strategy for achieving this goal. This would lead to the integration of lipids into the general focus of 21st Century biology; namely, into a fully quantitative systems-level biology.