Analysis of Lipids and Lipophillic Substances

描述（由申请人提供）：本申请要求提供资金以购买操作LC/MS/MS仪器所需的Applied Biosystems MDS SCIEX 4000 QTRAP三重四极杆质谱仪和Agilent 1200 LC系统。该仪器将用于一个新的脂质分析核心实验室，该实验室将在哥伦比亚大学欧文临床和转化研究所的机构资金和其他承诺的帮助下建立，该研究所是我们NIH资助的临床转化科学奖的所在地。LC/MS/MS脂质分析核心实验室将由来自哥伦比亚大学两个单位、内外科医师学院和Lamont-Doherty地球观测站的13名NIH资助的研究者（用户组成员）以及来自纽约城市学院生物系的1名研究者使用。脂质在慢性疾病的预防和发展中起着重要作用。人们越来越认识到，脂质，特别是许多以非常低的浓度（nM范围或更低）存在的脂质，在维持正常健康和慢性疾病（包括心血管疾病，癌症，糖尿病，肝病和神经系统疾病）的发展中起着关键作用。为了解开脂质代谢和行动之间的联系，并确定这些脂质如何保持慢性疾病预防和慢性疾病发展之间的平衡，现代研究实验室专注于脂质生理学和病理生理学必须能够评估低丰度，生物活性脂质的常规水平。至关重要的是，检测方法必须足够灵敏，以确定这些脂质的定性和定量性质在正常生理学和病理生理学之间的差异。我们计划购买的LC/MS/MS仪器将主要用于定量分析细胞、组织、生物液体和其他材料中含量极低的天然脂质和亲脂性物质，目的是了解这些生物活性脂质如何促进慢性疾病的发展和进展。我们申请的一个关键特征是包含一个试点项目计划，该计划将提供启动资金（每个奖项高达5，000美元），以开发新的协议（或扩展现有协议），使LC/MS/MS核心实验室能够获得额外的脂质分析协议，以添加到其分析服务列表中。我们建议资助8个试点项目，这些项目将推动额外分析方案的获取和开发。这将为核心实验室带来新的用户，并提高仪器对所有用户的价值。公共卫生相关性：脂质在所有主要慢性疾病的预防和发展中起着重要作用，包括心血管疾病、糖尿病、癌症、肝病和神经系统疾病。不同脂质在预防或引起慢性疾病方面的确切作用机制知之甚少。然而，已经确定的是，在细胞和组织中以非常低的水平存在的脂质具有作为信号传导分子的重要作用，并且由这些脂质分子产生的信号可以在慢性疾病预防和/或慢性疾病发展中发挥重要作用。组成我们用户组的研究人员的研究重点是解开脂质代谢和行动之间的联系，以及这些联系如何保持慢性疾病预防和慢性疾病发展之间的平衡。申请人拟购买的LC/MS/MS仪器将促进这项研究。

DESCRIPTION (provided by applicant): This application requests funds to purchase an Applied Biosystems MDS SCIEX 4000 QTRAP triple quadrupole mass spectrometer and an Agilent 1200 LC system needed for operation of the LC/MS/MS instrument. The instrument will be used in a new lipid analysis core laboratory that will be established with the help of institutional funds and other commitments from Columbia University's Irving Institute for Clinical and Translational Research, which is the home of our NIH- funded Clinical Translational Science Award. The LC/MS/MS lipid analysis core laboratory will be used by thirteen NIH-funded investigators (the User Group members) from two units of Columbia University, the College of Physicians and Surgeons and the Lamont-Doherty Earth Observatory and by an investigator from the Department of Biology of the City College of New York. Lipids play fundamental roles in the prevention and development of chronic diseases. There is growing awareness that lipids, specifically many that are present at very low concentrations (in the nM range or lower), play critical roles in both maintaining normal health and in the development of chronic diseases, including cardiovascular disease, cancer, diabetes, liver disease, and neurological diseases. In order to unravel linkages between lipid metabolism and actions, and to determine how these lipids maintain a balance between chronic disease prevention and chronic disease development, the modern research laboratory focused on lipid physiology and pathophysiology must be able to assess routinely levels of low abundance, bioactive lipids. It is critical that assays be sensitive enough to determine how the qualitative and quantitative nature of these lipids differs between normal physiology and pathophysiology. The LC/MS/MS instrument we are proposing to purchase will be used primarily to undertake quantitative analyses of natural lipids and lipophilic substances that are present at very low levels in cells, tissues, biological fluids and other materials with the goal of gaining understanding of how these bioactive lipids contribute to the development and progression of chronic diseases. A key feature of our application is the inclusion of a Pilot Project Program that will provide start- up funds (up to $5,000 per award) to develop new protocols (or extend existing ones) to enable the LC/MS/MS core laboratory to acquire additional lipid analysis protocols to add to its list of analytical services. We propose to fund 8 Pilot Projects that will drive the acquisition and development of additional analytical protocols. This will bring new users to the core laboratory and enhance the value of the instrument for all users. PUBLIC HEALTH RELEVANCE: Lipids have fundamental roles in both the prevention and the development of all of the major chronic diseases, including cardiovascular disease, diabetes, cancer, liver disease, and neurological disease. The precise mechanisms of action of different lipids in preventing or causing chronic diseases are poorly understood. It is however well established that lipids present at very low levels in cells and tissues have important roles as signaling molecules and that the signals generated by these lipid molecules can play significant roles in chronic disease prevention and/or chronic disease development. The research of the investigators who constitute our User Group is focused on unraveling linkages between lipid metabolism and actions, and how these linkages maintain a balance between chronic disease prevention and chronic disease development. The LC/MS/MS instrument proposed for purchase by the application will facilitate this research.