Analysis of Lipids and Lipophillic Substances

描述(申请人提供)：本申请申请资金用于购买一台应用生物系统公司的MDS SCIEX 4000 QTRAP三重四极杆质谱仪和一台安捷伦1200 LC系统，这是操作LC/MS/MS仪器所需的。该仪器将用于一个新的脂质分析核心实验室，该实验室将在机构资金和哥伦比亚大学欧文临床与翻译研究所的其他承诺的帮助下建立，该研究所是我们NIH资助的临床翻译科学奖的所在地。LC/MS/MS脂质分析核心实验室将由美国国立卫生研究院资助的13名研究人员(用户组成员)使用，这些研究人员来自哥伦比亚大学的两个单位：内科和外科医生学院和拉蒙特-多尔蒂地球天文台，以及来自纽约城市学院生物系的一名研究人员。血脂在慢性病的预防和发展中起着基础性作用。人们越来越意识到，脂质，特别是许多存在于极低浓度(在NM范围或更低)中的脂质，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)的发展中发挥着关键作用。为了揭示脂类代谢和作用之间的联系，并确定这些脂类如何在慢性病预防和慢性病发展之间保持平衡，专注于脂类生理学和病理生理学的现代研究实验室必须能够对低丰度、生物活性的脂类进行常规评估。至关重要的是，分析要足够灵敏，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有何不同。我们建议购买的LC/MS/MS仪器将主要用于对细胞、组织、生物液和其他材料中存在的极低水平的天然脂类和亲脂物质进行定量分析，目的是了解这些生物活性脂类如何促进慢性病的发展和进展。我们的应用程序的一个关键特征是包括一个试点项目计划，该计划将提供启动资金(每个奖项最高可达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更多的脂质分析协议，并将其添加到其分析服务清单中。我们建议为8个试点项目提供资金，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。与公共卫生相关：血脂在所有主要慢性疾病的预防和发展中都发挥着重要作用，包括心血管疾病、糖尿病、癌症、肝病和神经系统疾病。不同脂类在预防或引起慢性病方面的确切作用机制还知之甚少。然而，众所周知，存在于细胞和组织中的极低水平的脂类具有重要的信号分子作用，并且这些脂类分子产生的信号可以在慢性病预防和/或慢性病发展中发挥重要作用。构成我们用户组的研究人员的研究重点是解开脂代谢和行动之间的联系，以及这些联系如何在慢性病预防和慢性病发展之间保持平衡。应用程序建议购买的LC/MS/MS仪器将促进这一研究。

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.