Core A - Administration Core

摘要：核心A 该项目资助的中心假设是HDL的平台蛋白apoA-I是一种高密度脂蛋白， 构象动态支架，促进其他HDL蛋白和脂质重塑之间的相互作用 对动脉壁产生强有力的生物效应的因素。我们的目标是使多学科 团队了解，在前所未有的细节，HDL的结构，功能，组装和动力学，包括 使apoA-I作为平台发挥作用的分子机制。我们建议的研究项目中心 关于三个主题：项目1：HDL装配的结构基础-Jere Segrest，项目负责人（UAB）;项目2： HDL成熟的结构基础― ―W.肖恩戴维森，项目负责人（美国）。辛辛那提）;项目3：结构 HDL功能的基础- Jay Heinecke，项目负责人（U。华盛顿）。这三个主题涉及动态 四位世界级科学家之间的互动，他们拥有独特的（和互补的）专业知识领域， HDL是一种独特的合作，不太可能存在于任何单一的机构，在科学和HDL领域也很少见。 每个项目都提出了几个项目之间的合作研究，这些研究在2010年是不可能的。 没有PPG。所有项目都将广泛使用四个核心，这是PPG的关键组成部分： 核心A：管理-Jere Segrest（UAB），核心负责人;核心B：计算生物学-Martin Jones (UAB)，核心负责人;核心C：HDL定量和功能-Tomas Vaisar，核心负责人（U。华盛顿）; 核心D：蛋白质的产生和相互作用-W。肖恩戴维森，核心领导人（美国）。辛辛那提）。的 行政核心将指导该计划，评估科学进展，促进 调查员，并为整个计划和个人提供行政和预算支持 项目负责人和核心领导人。由于这个复杂的PPG涉及三个独立的项目和核心， 机构（UAB，U.辛辛那提和U.华盛顿）和第四家机构的一名额外合作研究者 （劳伦斯伯克利实验室），我们必须建立强有力的机制，以确保我们广泛的 在供资期间，在适当的外部咨询投入和财政监督下，继续进行互动。到 为了实现研究者和机构之间的必要整合，我们提出了以下具体目标：1。 应用最新的多研究者会议技术，在整个非洲大陆交流详细的 真实的时间的研究成果和想法; 2.建立文件共享、档案管理和 为所有调查员维持一个共同日历; 3.协调和资助一年两次的 PD和co-I; 4.通过建立和协调下列会议，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， UAB申请机构以外的项目和核心，通过每季度向U. 辛辛那提，美国华盛顿和劳伦斯伯克利实验室，并进行季度审查，他们的 平衡。

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.