Cell Biology and Functional Analysis Core for Institution # 269291

机构细胞生物学和功能分析核心

• 批准号: 10475411
• 负责人: Ilker Kudret Sariyer
• 金额: $ 25万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-05 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10475411
• 关键词: 3-Dimensional; Action Potentials; Area; Astrocytes; Award; Biological Assay; Blood Cells; Brain; Brain region; Cell Culture Techniques; Cell Line; Cell Survival; Cell physiology; Cells; Cellular biology; Central Nervous System Diseases; Cerebrum; Clinical; Collaborations; DNA; Data; Development; Disease; Electrophysiology (science); Endothelial Cells; Ensure; Fluorescent in Situ Hybridization; Funding; Goals; HIV; HIV-1; HIV-2; Histologic; Histology; Human; Image; Image Analysis; Imaging Techniques; Immune; In Vitro; Individual; Infection; Institution; Label; Maintenance; Mammalian Cell; Mentorship; Methods; Microelectrodes; Microglia; Microscopic; Microscopy; Mission; Modeling; Molecular; Morphology; Neurologic Deficit; Neurons; Neuropathogenesis; Neurosciences; Neurosphere; Oligodendroglia; Organoids; Patients; Physiological; Preparation; Primary Cell Cultures; Procedures; Process; Reagent; Regimen; Reproducibility; Research; Research Personnel; Resources; Rest; Risk; SIV; Scientist; Services; Site; T-Lymphocyte; Technical Expertise; Techniques; Technology; Therapeutic; Training; Translational Research; Viral; Viral Load result; Viral Vector; Virus; Virus Inhibitors; Virus Latency; Work; antiretroviral therapy; base; biomarker discovery; brain cell; brain endothelial cell; combat; data acquisition; design; experimental study; genetic manipulation; histological image; in vivo; induced pluripotent stem cell; innovation; interest; macrophage; microscopic imaging; multidisciplinary; nerve stem cell; neuroAIDS; neurocognitive disorder; neurotransmission; neurotropic virus; novel; programs; success; tissue processing; tool; viral rebound; virtual

SUMMARY The overall goal of the Cell Biology and Functional Analyses (CBFA) core is to provide basic scientists as well as clinical researchers studying HIV-1 induced neurological deficits at cell and molecular levels, resources, mentorship, and training. In addition, resources would be available to researchers transitioning to the area of NeuroHIV. Despite the success of the currently used antiretroviral therapy (ART) in controlling viral load in virtually all HIV-1 patients, this cocktail of viral inhibitors has not been able to eliminate the virus from latently infected cells including T-cells, macrophages, brain microglial cells, and cells in other sites of latency throughout the body. Therefore, the individuals remain at risk of viral rebound once they stop ART regimen. In the recent years, several strategies have been implemented to remove/edit viral sequences from the latently infected reservoirs. Equally as important is to be able to identify such cells to target and destroy them. The CBFA core is designed to provide investigators with training and technical expertise to utilize cellular and molecular tools to conduct research related to deciphering molecular mechanisms of HIV-1-induced CNS disease and ultimately design of molecular therapeutics to combat HIV-1 infection in the brain. This core would provide investigators with well characterized highly purified brain cells including neurons, astrocytes, oligodendrocytes, microglia, endothelial cells, and neural progenitors as well as cultured human peripheral blood cells for performing molecular, cellular, and virological studies. Moreover, human induced pluripotent stem cell (hiPSC) lines, and cortical spheroids and cerebral organoids from iPSCs, will be generated, characterized and made available for the core users in the field of NeuroHIV. In addition, expertise will be also provided for the isolation, characterization, propagation and maintenance of a variety of HIV-1 clades, HIV-2 and SIV. In this submission, we have included novel methods to study neuronal function in different regions of the brain using our Microelectrode Array (MEA) technology. In addition, expertise and training in microscopical, immunohistochemical analyses are offered to investigators. Our core will work closely with the other cores to promote a comprehensive multidisciplinary collaborative center program. This synergistic approach will ensure the success of CNHC developmental award recipients and CNHC users in conducting productive high impact research in neuroHIV. The main strength of our program is our team of experts with complementary expertise for investigators to conduct their neuroHIV research while working closely with the viral vector facility, and ultimately performing experiments in highly purified CNS cell cultures to assess the functional aspects of neuronal cells both in vitro and ex vivo.

总结 细胞生物学和功能分析（CBFA）核心的总体目标是提供基础科学家以及 作为在细胞和分子水平上研究HIV-1诱导的神经缺陷的临床研究人员，资源， 指导和培训。此外，将向过渡到以下领域的研究人员提供资源： 神经HIV尽管目前使用的抗逆转录病毒疗法（ART）在控制病毒载量方面取得了成功， 几乎所有的HIV-1患者，这种病毒抑制剂的鸡尾酒还没有能够消除病毒从潜伏 感染的细胞，包括T细胞、巨噬细胞、脑小胶质细胞和整个潜伏期的其他部位的细胞 身体因此，一旦停止ART方案，个体仍有病毒反弹的风险。近 多年来，已经实施了几种策略来从潜伏感染的细胞中去除/编辑病毒序列， 水库同样重要的是能够识别这些细胞，以瞄准并摧毁它们。CBFA的核心是 旨在为研究人员提供培训和技术专业知识，以利用细胞和分子工具， 进行与破译HIV-1诱导的CNS疾病的分子机制相关的研究，并最终 设计分子疗法来对抗大脑中的HIV-1感染。这个核心将为调查人员提供 用充分表征的高度纯化的脑细胞，包括神经元，星形胶质细胞，少突胶质细胞，小胶质细胞， 内皮细胞和神经祖细胞以及培养的人外周血细胞， 分子、细胞和病毒学研究。此外，人诱导多能干细胞（hiPSC）系，和 来自iPSC的皮质球状体和脑类器官将被生成、表征并可用于 NeuroHIV领域的核心用户。此外，还将提供隔离方面的专业知识， 本发明涉及多种HIV-1进化枝、HIV-2和SIV的表征、繁殖和维持。在这份呈件中， 我们已经包括了新的方法来研究神经元功能在不同地区的大脑使用我们的 微电极阵列（MEA）技术。此外，在显微镜， 免疫组织化学分析提供给研究者。我们的核心将与其他核心密切合作， 推动多学科综合协作中心项目。这种协同方法将确保 CNHC发展奖获得者和CNHC用户在开展生产性高影响方面的成功 neuroHIV的研究我们计划的主要优势是我们的专家团队具有互补的专业知识 研究人员在与病毒载体设施密切合作的同时进行神经HIV研究， 最终在高度纯化的CNS细胞培养物中进行实验，以评估 体外和离体的神经元细胞。