METABOLIC ANALYSIS INSTRUMENTATION TO ENHANCE TARGETED THERAPEUTICS STUDIES

南卡罗来纳州大学的COBRE靶向治疗中心（CTT）支持 旨在开发针对各种疾病的新的和更有效的药物类别的研究， 这些药物作用于在疾病中起关键作用的分子和细胞靶点。许多治疗靶点， 不同的疾病调节细胞代谢或在功能上受细胞代谢影响。审问的能力 这些靶点的遗传或药理学调节的代谢效应对许多CTT附属的 investigators.本提案旨在获得Agilent Seahorse细胞外通量（XF）分析仪， 包括便于数据成像和标准化的模块。这将取代旧版本的 无法执行高含量成像分析且不再受 制造商该仪器将属于CTT的显微镜和流式细胞术核心， 由一位在细胞代谢研究方面经验丰富的研究人员监督。有几个实验室， 包括前任和现任CTT资助的研究人员，他们将能够使用代谢分析， 工具，以提高他们的能力，以实现其研究目标。CTT下属的一些项目 立即需要Seahorse分析仪的研究人员调查（i）代谢物的影响 衍生的蛋白质修饰对神经退行性疾病的影响（ii）HIV相关变化的代谢效应， 脑小胶质细胞，（iii）神经传递中年龄相关变化的代谢分析，（iii）转录的影响 介体激酶对细胞代谢的影响，（iv） 递送治疗剂以支持组织再生。购买这一仪器将使继续进行 这些有针对性的治疗项目，并将提供一个更可靠的方式来使用所获得的数据。的能力 测量细胞代谢反应和适应将加强目前CTT支持的项目， 将允许CTT将其保护伞扩展到其他靶向治疗研究人员， 结合代谢分析。

The COBRE Center for Targeted Therapeutics (CTT) at the University of South Carolina (UofSC) supports research that seeks to develop new and more effective classes of drugs against various diseases, by aiming these drugs at molecular and cellular targets that play a key role in the disease. Many therapeutic targets in different diseases either regulate or are functionally impacted by cellular metabolism. The ability to interrogate the metabolic effects of genetic or pharmacological modulation of such targets is critical to many CTT-affiliated investigators. The purpose of this proposal is to acquire an Agilent Seahorse Extracellular Flux (XF) Analyzer, including a module to facilitate data imaging and normalization. This will replace an older version of this instrument that cannot perform the high content imaging analyses and is no longer supported by the manufacturer. This instrument will belong to the Microscopy and Flow Cytometry Core of the CTT and will be overseen by a highly experienced investigator in cellular metabolic studies. There are several laboratories, including former and present CTT-funded investigators, which will be able to use the metabolic analysis instrument to increase their ability to achieve their research goals. Some of the projects by CTT-affiliated investigators that have an immediate need for the Seahorse Analyzer to investigate (i) the impact of metabolite derived protein modifications on neurodegenerative diseases (ii) metabolic effects of HIV-related changes in brain microglia, (iii) metabolic analysis of age-related changes in neurotransmission, (iii) effects of transcriptional Mediator kinase on cellular metabolism, (iv) cellular metabolic effects of nanoparticle and scaffold implants that deliver therapeutics to support tissue regeneration. Acquisition of this instrument will allow the continuation of these targeted therapeutics projects and will offer a more reliable way to use the data acquired. The capacity to measure cellular metabolism responses and adaptations will enhance the current CTT-supported projects and will allow CTT to extend its umbrella to other targeted therapeutics researchers whose research areas incorporate metabolic analyses.