R21 Planning Grant for the CCTRHIB Program

描述(由申请人提供)：此申请是为CCTRHIB项目提供的R21规划补助金。在这笔赠款的一年任期内，我们将实现三个目标。首先，我们将组织临床和研究人员进入一个致力于研究人类对感染性病原体的免疫反应的中心。我们将强调并鼓励针对有可能成为生物恐怖分子的微生物开展工作。该中心的组织工作将包括创建研讨会系列、正在进行的工作系列和期刊俱乐部。在纽约科学院举行的一年两次的研讨会将包括一次专门讨论人类免疫和生物恐怖分子的会议。在这一年里，我们将开发翻译中心的理论基础和研究设计。根据目前的设想，该中心将致力于与病毒蛋白有关的技术和研究，这些蛋白具有阻断先天免疫或启动特定免疫的功能。预计将通过这种类型的研究收集信息，以便开发用于疫苗的突变病毒。此外，病毒基因将被插入活病毒载体中，并在人类细胞系统中测试其免疫原性和先天免疫刺激活性。为了与该中心目前的理论基础保持一致，人类原代细胞将用于先天免疫和特异性免疫启动的检测。在R21的任期内，我们将开发从不同目标组织收集和生长人类上皮细胞的技术。我们还将寻找可能的组织来源，以便培养不同年龄、性别和种族的患者的细胞。还将开发大规模培养树突状细胞的技术。病毒制剂、突变病毒或已开发的含有病毒基因的载体将在这些细胞中进行测试，以确定它们对DC成熟的影响。此外，受感染的DC将接受使用人类T细胞刺激免疫反应的能力测试。这项工作的目的是建立一个具有共同兴趣和目标的研究人员互动小组，以导致提交U19赠款，以创建一个致力于研究人类免疫学和可能被用作生物恐怖分子的微生物的翻译中心。

DESCRIPTION (provided by applicant): This application is for an R21 Planning Grant for the CCTRHIB program. During the one-year tenure of this grant, we will accomplish three aims. First we will organize clinical and research investigators into a center dedicated to the study of human immune responses to infectious agents. We will emphasize and encourage the work to be aimed at microbes with the potential as bioterrorist agents. Organization of the center will included the creation of a seminar series, work in progress series and a journal club. A session devoted to human immunity and bioterrorist agents will be included in a twice yearly symposium at the New York Academy of Sciences. During this year we will develop the rationale and research design for the Translational Center. As currently envisioned the center will be devoted to the development of technology and research relating to viral proteins which function to block innate immunity or the initiation of specific immunity. It is expected that through studies of this type information will be gathered that will allow the development of mutant viruses for use as vaccines. Additionally, viral genes will be inserted into live virus vectors and tested for their immunogenicity and innate immune stimulating activity in human cell systems. In keeping with the current rationale of the center, human primary cells will be used in assays of both innate and the initiation of specific immunity. During the tenure of the R21 we will develop techniques for collecting and growth of human epithelial cells from different target tissue. We will also locate possible sources of tissue in order to grow cells from patients of varying age, sex, and ethnicity. Techniques for large-scale growth of dendritic cells will also be developed. The viral agents, mutant viruses or developed vectors containing viral genes will be tested in these cells to determine their effects on the maturation of DCs. Additionally, the infected DC will be tested for their ability to stimulate immune responses using human T cells. This work is aimed to develop an interactive group of investigators with common interests and goals that will lead to the submission of a U19 grant for creation of a Translational Center devoted to the study of Human Immunology and microbes with the potential to be used as bioterrorist agents.