Scientific Core: Peptide and DNA technology core

科学核心：肽和DNA技术核心

• 批准号: 7290992
• 负责人: Joachim Spiess
• 金额: $ 36.16万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7290992
• 关键词: biomedical facility; cooperative study; gene deletion mutation; genetic markers; genetically modified animals; in situ hybridization; interdisciplinary collaboration; laboratory mouse; minority institution research support; neurobiology; neurosciences; oligonucleotides; peptide chemical synthesis; peptides; transfection /expression vector

The theme of this program proposal is the genetic, cellular and systemic mechanisms of cognitive processes, mainly learning and memory und their modulation by stress, anxiety and neuromodulators such as the peptide hormone corticotropin-releasing factor (CRF) or drugs such as methamphetamine. The participating projects address clinical and physiologic aspects. Since all projects use animal models, mouse or rat models, or converge at such models, a Core will be established that will support the projects with transgenic mice which are already available or have to be produced, with synthetic neuropeptides that have been already designed or have to be developed, polyclonal antibodies against selected peptides or overexpressed proteins. The Core will also provide assistance in the design of oligonucleotides for the screening of cohorts that are available or will be generated by the Projects, for in situ hybridizations or for interference with transcription or translation. It will also assist in the application procedure of drugs, especially peptides, in animal experiments. In addition to the mentioned support, the Core will contribute to the development of transgenic technology with the final goal to induce acute gene deletions at defined sites of the mouse brain. A special focus will be on the development of viral vectors to apply DNA constructs to selected sites in the rodent brain with the objective to induce the deletion of a targeted gene or to inhibit translation. The clinical relevance of this Core is based on its support of screening of patient cohorts with genetic markers and the development of such markers.

这项计划提案的主题是认知过程的遗传、细胞和系统机制，主要是学习和记忆以及压力、焦虑和 神经调节剂，如多肽激素促肾上腺皮质激素释放因子(CRF)或药物，如甲基苯丙胺。参与的项目涉及临床和生理方面。由于所有项目都使用动物模型、小鼠或大鼠模型或汇聚在这些模型上，将建立一个核心项目，以支持已有或必须生产的转基因小鼠、已经设计或必须开发的合成神经肽、针对选定多肽或过度表达的蛋白质的多克隆抗体的项目。该核心还将在设计寡核苷酸方面提供协助，以筛选项目现有或将产生的队列，用于原位杂交或干扰转录或翻译。它还将帮助药物，特别是多肽，在动物实验中的应用程序。除了上述支持外，Core还将为转基因技术的发展做出贡献，最终目标是在小鼠大脑的特定部位诱导急性基因缺失。一个特别的重点将是开发病毒载体，将DNA构建应用于啮齿动物大脑中选定的位置，目的是诱导目标基因的缺失或抑制翻译。 这一核心的临床相关性是基于它对具有以下特征的患者队列的筛查支持 遗传标记和此类标记的发展。