CORE--BIOCHEMICAL CORE

核心--生化核心

• 批准号: 6732372
• 负责人: PIETRO P SANNA
• 金额: $ 15.51万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-13 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732372
• 关键词: Adenoviridae; GABA receptor; Herpesviridae; NMDA receptors; alcoholism /alcohol abuse; biochemistry; biomedical facility; biotechnology; gamma aminobutyrate; gene expression; neuropeptide Y; transfection /expression vector

DESCRIPTION (provided by applicant): The biochemical core primary objectives are to develop and provide viral vectors for the overexpression of neuropeptides or for the delivery of antisense sequences to such peptides or their receptors, and to synthesize and measure neurosteroids for investigators in the TSRI-ARC and Center at Large. The viral vector Component will serve as a service unit for the development and production of viral vectors for investigators in the TSRI-ARC and Center at Large. The core will generate the vector constructs, package and expand the vectors, and evaluate vector gene transduction efficiency and levels of expression. The use of viral vectors is of interest to the ARC components directed by Drs. Rivier, Weiss, and Zorrilla (pilot), as well as for Dr. Ehlers and Dr. Koob NIAAA-supported research. All these investigators plan to use viral vectors for the modulation (up/down-regulation) of the expression of the neuropeptides NPY, CRF and their receptors. The centralization of these activities in the present core will allow for the systematic characterization of the most advantageous vector/promoter combinations for transgene delivery and expression in brain regions relevant to alcohol's actions and for the cost-effective and efficient production of such vectors. The neurosteroid component serves as a service unit for the synthesis and measurement of neuroactive steroids for investigators in the TSRI-ARC and Center at Large. Neuroactive steroids are potent neuromodulators, some of which (termed neurosteroids) are synthesized by the nervous system from cholesterol or derived from metabolites of steroid hormones of endocrine gland origin, such as progesterone or deoxycorticosterone. The primary objectives of this component will be to synthesize and purify neurosteroids for use by TSRI-ARC and Center at Large investigators, including Drs. Craig Slawecki, Friedbert Weiss, George Siggins, and Karen Britton. This component will also coordinate the tissue collection, processing, and measurement of neurosteroids by GC/MS in alcohol-related investigations at TSRI; and develop new syntheses for neurosteroid derivatives that interact with GABAA-receptors and NMDA-receptors involved in alcohol preference in alcohol-dependent animals provided by the Animal Core.

描述（由申请人提供）：生化核心主要目标是开发和提供用于神经肽过表达或用于将反义序列递送至此类肽或其受体的病毒载体，以及为 TSRI 的研究人员合成和测量神经类固醇ARC 和大型中心。病毒载体组件将作为一个服务单元，为 TSRI-ARC 和大型中心的研究人员开发和生产病毒载体。核心将生成载体构建体，包装和扩展载体，并评估载体基因转导效率和表达水平。病毒载体的使用引起了 ARC 组件的兴趣，由 Drs. 指导。 Rivier、Weiss 和 Zorrilla（试点），以及 Ehlers 博士和 Koob 博士 NIAAA 支持的研究。所有这些研究人员计划使用病毒载体来调节（上调/下调）神经肽 NPY、CRF 及其受体的表达。这些活动集中在本核心中，将允许系统地表征最有利的载体/启动子组合，用于与酒精作用相关的大脑区域中的转基因递送和表达，并实现此类载体的成本效益和高效生产。 神经类固醇成分作为合成和测量的服务单元 为 TSRI-ARC 和大型中心的研究人员提供神经活性类固醇。神经活性类固醇是有效的神经调节剂，其中一些（称为神经类固醇）由神经系统从胆固醇合成或衍生自内分泌腺来源的类固醇激素的代谢物，例如黄体酮或脱氧皮质酮。该组件的主要目标是合成和纯化神经类固醇，供 TSRI-ARC 和大型研究中心的研究人员使用，包括 Drs.克雷格·斯拉维克、弗里德伯特·韦斯、乔治·西金斯和凯伦·布里顿。该组件还将协调 TSRI 在酒精相关研究中通过 GC/MS 进行的组织采集、处理和神经类固醇测量；并开发神经类固醇衍生物的新合成方法，这些衍生物与 Animal Core 提供的酒精依赖动物中参与酒精偏好的 GABAA 受体和 NMDA 受体相互作用。