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中文摘要
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 描述(申请人提供):人类遗传学和基因组编辑的快速发展为开发不同人类疾病的动物模型创造了前所未有的科学机会。然而,这些机会已经使哥伦比亚大学医学中心(CUMC)的动物设施严重紧张。这一申请反映了CUMC对提高动物护理和福利质量的坚定承诺,以达到或超过PHS关于保护和使用实验动物的政策。由于预计将集中精力研究神经疾病,这个专注于疾病研究的神经生物学及其翻译以促进人类健康的项目,将在现有的CUMC动物设施内升级和装备1365平方英尺的面积,作为建立高通量啮齿动物行为分析核心的努力的一部分。这个改进后的设施将包括专门的啮齿动物住所的屏障空间,活体动物手术和病毒载体注射的动物准备和性能,以及行为测试。具体地说,该提案寻求联邦资金,用于购买三个单HEPA过滤通风笼架和四个双HEPA过滤通风笼架、四个HEPA过滤通风更换和转运站以及一个生物安全柜。还将要求支付与安装和连接通风机架和生物安全柜有关的相关建造费用。我们在这里建立的设施将使CUMC的研究人员能够抓住遗传学和基因组工程进步带来的机遇,同时仍然提供非常高标准的动物护理、福利和人类安全。为了与此保持一致,所要求的设备将使我们能够完成三个具体的 目标:(1)最大限度地提高专门的啮齿动物收容所的容量;(2)最大限度地减少环境变化对动物行为的影响,并最大限度地减少人类在更换笼子和实验操作动物时接触到啮齿动物过敏原和破坏群体生物安全的风险;以及(3)允许进行无菌生存手术和安全地将病毒载体注射到动物体内,以实现最佳质量的研究。这项建议代表了CUMC为满足其疾病社区神经生物学目前和预期的需求而做出的关键和实质性的努力,它为啮齿动物(主要是小鼠)提供了一个新的、全功能的屏障行为测试设施。认识到这一努力的重要性,院长办公室、哥伦比亚转化神经科学倡议和基因组医学研究所联合起来,共同提供所有必要的支持,以创建上述设施,超出这笔赠款所能提供的资源。这一机构承诺将包括:(1)将新设施的翻新/建设成本整合到CUMC比较医学研究所正在进行的旨在升级其动物护理设施的资本项目中,以及(2)涵盖所有行为测试仪器的购买。
英文摘要
 DESCRIPTION (provided by applicant): Rapid advances in human genetics and in genome editing are creating unprecedented scientific opportunities to develop animal models of different human diseases. These opportunities, however, are already severely straining the animal facilities at Columbia University Medical Center (CUMC). This application reflects the deep commitment of the CUMC to improving the quality of animal care and welfare necessary to meet or exceed PHS Policy on the Care and Use of Laboratory Animals. Because of the expected concentration of efforts in neurological disorders, this project, which focuses on neurobiology of disease research and its translation to advance human health, will upgrade and equip a 1,365 square foot area within the existing CUMC animal facility as part of an effort to establish a high-throughput rodent behavior analysis core. This improved facility will be comprised of barrier-space for dedicated rodent housing, animal preparation for and performance of live animal surgery and viral vector injections, and behavioral testing. Specifically, the proposal seeks Federal funds for the purchase of three single and four double HEPA-filtered ventilated cage racks, four HEPA-filtered ventilated changing and transfer stations, and one biosafety cabinet. Associated construction costs related to the installation and connection of the ventilated racks and the biosafety cabinet will also be sought. The facility we establish here will allow CUMC investigators to seize the opportunities created by advances in genetics and genome engineering, while still providing for the very highest standards of animal care and welfare and human safety. In keeping with this, the requested equipment will allow us to fulfill three Specific Aims: (1) to maximize the dedicated rodent housing capacity; (2) to minimize the effects of environmental changes on animal behaviors and to minimize the risk of harmful human exposure to rodent allergens and breaks in colony biosecurity during cage changes and experimental manipulation of animals; and, (3) to allow the sterile performance of survival surgery and safe injection of viral vectors into animals to achieve optimal quality research. This proposal represents CUMC's critical and substantial effort to meet the present and anticipated needs of its neurobiology of disease community by providing a new and fully-functional barrier behavioral testing facility for rodents (primarily mice). Recognizing the importance of this effort the Dean's office, the Columbia Translational Neuroscience Initiative, and the Institute of Genomic Medicine have come together to collectively provide all of the necessary support to create the facility described above beyond the resource that this grant would provide. This institutional commitment will include: (1) integrating the costs of renovation/construction of the new facility into the ongoing capital project of CUMC's Institute of Comparative Medicine aimed at upgrading its animal care facilities and (2) covering the purchase of all of the behavior testin apparatii.
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Circuit-specific, chemogenetic neuromodulation in nonhuman primates.
A multiplexable in vivo perturbation toolkit to identify genes affecting neurodegeneration in a model of synucleinopathy
Defining Immune Cell Heterogeneity in Human ALS and Mouse Model of the Disease
Defining immune cell heterogeneity in human ALS and mouse model of the disease
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