UC Davis/NIH NeuroMab Facility

加州大学戴维斯分校/NIH NeuroMab 设施

• 批准号: 8113160
• 负责人: James S Trimmer
• 金额: $ 139.49万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8113160
• 关键词: Adult; Antibodies; Antigens; Area; Biochemical; Brain; Cells; Clinical; Communities; Data; Diagnostic Procedure; Equipment and supply inventories; Future; Generations; Genes; Human Genome; Hybridomas; Immunization; Immunoglobulin G; Libraries; Mission; Monoclonal Antibodies; Neurons; Neurosciences; Neurosciences Research; Post-Translational Protein Processing; Preparation; Proteins; Protocols documentation; Reagent; Recombinants; Relative (related person); Research; Research Personnel; Specificity; Synthetic Vaccines; Therapeutic; United States National Institutes of Health; aged; cost; mouse genome; novel; protein protein interaction; public health relevance; rat genome; tissue culture

DESCRIPTION (provided by applicant): The specific aim of this proposal is to continue the mission of the UC Davis/NIH NeuroMab Facility: to develop a comprehensive library of monoclonal antibodies (mAbs) optimized for use in the brain (i.e. NeuroMabs). This renewal remains driven by the need, articulated in the original proposal to create the UC Davis/NIH NeuroMab Facility, and that still remains, to greatly expand the availability of such brain-optimized mAbs for use in basic, translational and clinical neuroscience research. There remains a need for high- quality antibodies against defined gene products that serve as the crucial bridge between the inventory of genes expressed in the brain, and understanding how their products determine brain function in normal and pathological conditions. However, many necessary reagents remain either unavailable, or when available suffer from a lack of efficacy and specificity, especially when used in mammalian brain preparations. The availability of high-quality, reliable mAbs that have been optimized for use in mammalian brain (i.e. NeuroMabs) is of utmost importance to virtually all areas of neuroscience. We will continue to pursue the generation of a comprehensive library of NeuroMabs by using recombinant and/or synthetic immunogens corresponding to fragments of neuronal proteins in an intense immunization protocol that yields large numbers of IgG-secreting hybridomas from a relatively short immunization period. These large hybridoma pools will be screened for those mAbs that recognize the cognate antigen in heterologous cells, and then the entire positive pool subjected to comprehensive biochemical and immunohistochemical analyses of their efficacy and specificity in brain. The resultant brain-optimized NeuroMabs will continue to be made available at very low cost to the research community as tissue culture supernatants or as purifed IgG preparations. Investigators will continue to use these NeuroMabs for determining the presence and relative abundance of the cognate antigens in developing, adult, aged, and diseased brain, their cellular and subcellular localization, functionally relevant post-translational modifications, and protein-protein interactions. Moreover, NeuroMabs will continue to find additional applications in direct functional analyses of proteins, in diagnostic procedures, and as therapeutics. PUBLIC HEALTH RELEVANCE: The availability of high-quality, reliable mAbs that have been optimized for use in mammalian brain is of utmost importance to virtually all areas of basic, translational and clinical neuroscience.

描述（由申请人提供）：该提案的具体目的是继续执行UC Davis/NIH Neuromab设施的使命：开发用于在大脑中使用的全面单克隆抗体（MAB）的全面库（即Neuromabs）。这种更新仍然受到创建UC Davis/NIH Neuromab设施的原始提案所阐明的需求的驱动，并且仍然存在，以极大地扩展了此类脑部优化的MAB的可用性，以用于基础，翻译和临床神经科学研究。仍然需要针对定义的基因产物的高质量抗体，这些抗体是大脑中表达的基因库存之间的关键桥梁，并了解其产物如何在正常和病理条件下确定大脑功能。但是，许多必要的试剂要么不可用，要么在可用的情况下缺乏功效和特异性时，尤其是在哺乳动物脑部制备中使用时。用于在哺乳动物大脑中使用的高质量，可靠的mAB的可用性（即神经瘤）对于几乎所有神经科学领域都至关重要。我们将继续使用重组和/或合成免疫原子来追求与神经元蛋白片段相对应的强烈免疫接种方案中，从而产生大量的IgG杂交杂种，从而从相对较短的免疫时期中产生与神经元蛋白片段相对应的综合库。这些大型杂交瘤池将被筛选为那些识别异源细胞中同源抗原的mAB，然后将整个阳性池经过全面的生物化学和免疫组织化学分析，这些分析对其在大脑中的疗效和特异性进行了。最终的脑部优化神经瘤将继续以非常低的成本作为组织培养物上清液或净化的IgG制剂，以非常低的成本提供。研究人员将继续使用这些神经毛电图来确定同源抗原在发育，成人，老年和患病的大脑中的存在和相对丰度，它们的细胞和亚细胞定位，功能相关的翻译后修饰以及蛋白质 - 蛋白质相互作用。此外，Neuromabs将继续在蛋白质，诊断程序和作为治疗剂的直接功能分析中找到其他应用。 公共卫生相关性：用于在哺乳动物大脑中使用的高质量，可靠的单克值的可用性对于几乎所有基本，转化和临床神经科学的领域至关重要。