Research Administration Core, Human DNA Samples Bank, Animal Models, & Databases

描述(由申请者提供)：在过去18年的项目资助期间，我们在理解发作性睡病的病理生理学以及正常睡眠的生理学方面取得了重大进展。我们在上一次资助期间发现，大多数人类发作性睡病猝倒病例都是由下丘脑泌素(也称为食欲素)缺乏引起的，这一发现显着改变了睡眠领域。在这份修订后的竞争性续签提案中，我们根据我们最近的发现，重新调整了我们的研究努力，并招募了新的成员，以扩大中心的专业知识。在这份修订后的提案中，我们聚集了一组独特的独立调查人员，他们跨学科工作，朝着一个共同的目标努力。根据审查员的批评，我们从最初的提案中删除了两个项目，留下了四个项目和一个核心项目(项目A)。核心项目(项目A)提供必要的核心资源，以支持斯坦福大学发作性睡病研究中心的研究项目，尤其是生物样本。由麦迪逊威斯康星大学的Terry Young博士指导的B项目的目标是使用流行病学方法确定无猝倒的发作性睡病的患病率，并研究其与人类白细胞抗原(HLA)和溶血肌素缺乏症的关系。项目D由朱丽叶·法拉科博士指导，将使用斑马鱼模型分离调节下丘脑泌素和组胺神经传递的新基因。在项目F中，下丘脑分泌素的发现者Luis de Lecea博士正在寻求寻找在含有下丘脑分泌素的细胞中优先表达的新基因；该项目的一个附属目标将是研究无猝倒的发作性睡病的神经病理学。由Joachim Hallmayer博士指导的项目E将使用人类基因方法来识别新的发作性睡病易感基因。发作性睡病是一种常见的致残神经疾病，每2000名美国人中就有一人受到影响。我们最近的发现导致了新的诊断程序，但尚未改变治疗方案。我们的目标是改进诊断，更好地理解发作性睡病的病理生理学，并发现新的治疗方法，如果不能治愈发作性睡病患者的话。 项目A 少年派：伊曼纽尔·米诺特 标题：研究管理核心，人类DNA样本库，动物模型和数据库 描述(由申请人提供)：一支经验丰富且训练有素的研究管理人员对于有效管理一个复杂的多学科项目至关重要。在该项目连续18年的资助期间，睡眠研究中心的首席研究员和助理主任共同努力，建立了一支由研究管理员和研究支持人员组成的团队，负责管理发作性睡病中心的日常活动。这包括预算和财务报告规划、政策和指导方针的监督、动物和人体数据库管理、受试者招募以及将该项目整合到睡眠研究中心和睡眠诊所，以及总体上确保该计划顺利运行。为了支持这项修订后的研究提案，我们确认了五项主要核心活动：1)研究行政和协调职能，以促进研究人员和项目之间的研究和互动；2)本提案中使用的斯坦福大学嗜睡症动物群体中心的管理；这包括斑马鱼、小鼠和大鼠。3)为研究项目招募人类发作性睡病患者：包括收集发作性睡病患者和对照受试者的DNA、血清、脑脊液和脑标本。4)维护包含人类、小鼠/大鼠、犬类发作性睡病数据和组织样本数据的计算机化数据库；维护项目网站和在线数据共享。5)维护支持遵守所有联邦指导方针和政策进行研究的所有文件。首席调查员有责任确保发作性睡病科学家中心作为一个综合团队开展工作。他的指导和科学领导，对于追求该计划的总体目标至关重要。每周举行一次研究会议，以促进研究人员之间以及研究人员和研究行政人员之间的沟通。

DESCRIPTION (provided by applicant): During the last 18 years of funding of this program project, the only NIH supported program project focused on narcolepsy, we have made significant strides in understanding the pathophysiology of narcolepsy, as well as the physiology of normal sleep. Our discovery during the last funding period that most cases of human narcolepsy cataplexy are caused by hypocretin (also called orexin) deficiency significantly changed the sleep field. In this revised competitive renewal proposal, based on our recent discoveries, we have refocused our research efforts and recruited new members to expand the expertise of the Center. In this revised proposal, we have brought together a unique group of independent investigators working across disciplines toward a common goal. Based on the reviewers' critiques, we have removed two projects from our original proposal, leaving four projects and a core (Project A). The core (Project A) provides the necessary core resources to support research projects at the Stanford Center for Narcolepsy, most notably biological samples. The goal of Project B, directed by Dr. Terry Young at the University of Wisconsin, Madison is to determine the prevalence of narcolepsy without cataplexy using an epidemiological approach and to study its association with HLA and lypocretin deficiency. Project D, directed by Dr. Juliette Faraco, will use a zebrafish model to isolate novel genes regulating hypocretin and histamine neurotransmission. In Project F, directed by Dr. Luis de Lecea, the discoverer of hypocretins, is seeking to identify novel genes with preferential expression in hypocretin-containing cells; an accessory goal of this project will be to study the neuropathology of narcolepsy without cataplexy. Project E, directed by Dr. Joachim Hallmayer, will use a human genetic approach to identify novel narcolepsy susceptibility genes. Narcolepsy is a frequent and disabling neurological disorder affecting more than 1 in 2,000 Americans. Our recent findings have led to new diagnostic procedures but have not yet changed therapeutic options. Our aims are improved diagnosis, a better understanding of the narcolepsy pathophysiology and the discovery of new treatments, if not a cure for narcoleptic patients. PROJECT A PI: Emmanuel Mignot Title: Research Administration Core, Human DNA Samples Bank, Animal Models, & Databases Description (provided by applicant): A seasoned and well-trained research administration staff is essential for the effective management of a complex multi-disciplinary program project. During the last consecutive 18 years of funding of this program project the Principal Investigator and the Assistant Director of the Sleep Research Center have worked together and built a team of research administrators and research support staff that are responsible for the day-to-day activities of managing the Center for Narcolepsy. This includes budgetary and fiscal reporting planning, oversight of policy and guidelines, animal and human database management, subject recruitment and the integration of this project into the Sleep Research Center and Sleep Clinic, and in general ensuring that the program runs smoothly. To support this revised research proposal, five main core activities are recognized: 1) A research administrative and coordinating function to facilitate the research & interactions among investigators and projects 2) Management of the Stanford University Center for Narcolepsy animal colonies used in this proposal; this includes zebrafish, mice, and rats. 3) Recruitment of human narcolepsy patients for research projects: this includes the banking of DNA, serum, cerebrospinal fluid and brain specimens from narcolepsy and control subjects. 4) Maintenance of computerized databases containing human, mouse/rat, canine narcolepsy data and tissue sample data; maintenance of the project's website and data-sharing on-line. 5) Maintenance of all documentation supporting adherence to all federal guidelines and policies for conducting research. It is the responsibility of the Principal Investigator to assure that the Center for Narcolepsy scientists work as an integrated team. His direction and scientific leadership, is essential to the pursuit of the overall goals of the program. A weekly research meeting is held to facilitate communication among the investigators and between the research staff and research administration staff.