Core A - Administration Core

摘要：核心A 这个项目的中心假设是，高密度脂蛋白的平台蛋白apoA-I是一种 构象动态支架，促进其他高密度脂蛋白之间的相互作用和脂质重塑 对动脉壁施加强大生物效应的因子。我们的目标是让一个多学科的 团队将以前所未有的详细信息了解HDL语言的结构、功能、组装和动力学，包括 使apoA-I发挥平台作用的分子机制。我们建议的研究计划中心 关于三个专题：项目1：高密度脂蛋白汇编的结构基础--Jere Segrest，项目负责人(UAB)；项目2： 高密度脂蛋白成熟的结构基础--W.肖恩·戴维森，项目负责人(U·辛辛那提)；项目3：结构 高密度脂蛋白功能基础-Jay Heinecke，项目负责人(华盛顿大学)。这三个主题涉及到动态的 四位世界级科学家之间的互动，他们具有独特的(和互补的)专业领域，都在研究 这是一种独一无二的合作，在任何一个机构都不太可能存在，在科学和高密度脂蛋白领域也是罕见的。 每个项目都提出了几个项目之间的合作研究，这在 没有一个PPG。所有项目将广泛使用四个核心，这四个核心是PPG的关键组件： 核心A：行政-Jere Segrest(UAB)，核心领导者；核心B：计算生物学-Martin Jones (UAB)，核心领导者；核心C：高密度脂蛋白定量和功能--Tomas Vaisar，核心领导者(华盛顿大学)； 核心D：蛋白质生产和相互作用--W.肖恩·戴维森，核心领导者(U·辛辛那提)。这个 管理核心将指导该计划，评估科学进步，促进 调查人员，并为整个方案和个人提供行政和预算支助 项目负责人和核心负责人。由于这一复杂的PPG涉及三个独立的项目和核心 机构(加州大学伯克利分校、辛辛那提大学和华盛顿大学)和第四个机构的另一名联合调查员 (劳伦斯伯克利实验室)，我们必须建立健全的机制，以确保我们广泛的 在供资期间，在适当的外部咨询意见和财政监督的情况下，互动仍在继续。至 为了实现调查人员和机构之间所需的整合，我们提出了这些具体目标：1. 应用最新的多调查员会议技术，在整个大陆交流详细的 实时研究成果和想法；2.建立文件共享、文件管理和 维持所有调查员的共同日历；3.协调和资助委员会每年举行两次会议 PDS和共同信息系统；4.通过建立和协调以下会议，为外部科学投入提供机制 外部和内部咨询委员会和安排外部顾问；5.提供财政监督，以 UAB申请机构以外的项目和核心通过向美国政府发放季度分包合同。 辛辛那提、华盛顿大学和劳伦斯·伯克利实验室，并对其 余额。

ABSTRACT: CORE A The central hypothesis of this Program Project Grant is that HDL’s platform protein, apoA-I, is a conformationally dynamic scaffold that facilitates interactions among other HDL proteins and lipid remodeling factors that exert potent biological effects on the artery wall. Our objective is to empower a multidisciplinary team to understand, in unprecedented detail, HDL’s structure, function, assembly and dynamics, including the molecular mechanisms that enable apoA-I to function as a platform. Our proposed research program centers on three topics: Project 1: Structural basis of HDL assembly ―Jere Segrest, Project Leader (UAB); Project 2: Structural basis of HDL maturation ―W. Sean Davidson, Project Leader (U. Cincinnati); Project 3: Structural basis of HDL function – Jay Heinecke, Project Leader (U. Washington). These three topics involve the dynamic interactions among four world-class scientists with unique (and complementary) areas of expertise all studying HDL, a unique collaboration unlikely to exist at any single institution and rare in science and in the HDL field. Each project has proposed several collaborative studies among projects that would not be possible in the absence of a PPG. All projects will make extensive use of four Cores, which are key components of the PPG: CORE A: Administration―Jere Segrest (UAB), Core Leader; CORE B: Computational biology―Martin Jones (UAB), Core Leader; CORE C: HDL quantitation and function―Tomas Vaisar, Core Leader (U. Washington); CORE D: Protein production and interaction―W. Sean Davidson, Core Leader (U. Cincinnati). The Administrative Core will direct the program, evaluate scientific progress, facilitate interactions among investigators, and provide administrative and budgetary support to the Program as a whole and individual Project Leaders and Core Leaders. Since this complicated PPG involves projects and cores at three separate institutions (UAB, U. Cincinnati, and U. Washington) and one additional co-investigator at a fourth institution (Lawrence Berkley Laboratories), we must establish robust mechanisms to ensure that our extensive interactions continue during the funding period, with appropriate outside advisory input and fiscal oversight. To achieve the required integration between investigators and institutions, we propose these specific aims: 1. Apply the latest in multi-investigator conferencing technology to exchange, across the continent, detailed research results and ideas in real time; 2. Establish mechanisms for document sharing, file management and maintenance of a common calendar for all investigators; 3. Coordinate and fund twice-yearly meetings of the PDs and co-Is; 4. Provide mechanisms for outside scientific input by establishing and coordinating meetings of External and Internal Advisory Committees and arranging for outside consultants; 5. Provide fiscal oversight to the projects and cores outside the Applicant Institution of UAB by issuing quarterly subcontracts to U. Cincinnati, U. Washington and Lawrence Berkley Laboratories, and by conducting quarterly reviews of their balances.