ShEEP Request for Intracellular and Extracellular Protein Signaling Station (IEPSS)

ShEEP 请求细胞内和细胞外蛋白质信号转导站 (IEPSS)

• 批准号: 10178936
• 负责人: Bruce R. Troen
• 金额: --
• 依托单位: VA WESTERN NEW YORK HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10178936
• 关键词: Acinetobacter baumannii; Acute; Age related macular degeneration; Aging; Antioxidants; Biological Markers; Cardiac; Catalytic RNA; Cell Death; Cell Separation; Cells; Charge; Chronic; Clinical Research; Collaborations; Collection; Cultured Cells; DNA Methylation; Data; Detection; Development; Devices; Disease; Epithelial Cells; Equipment; Extracellular Protein; Functional disorder; Funding; Future; Gel; Health; Heart Arrest; Hematopoietic; Hour; Human; Image; Immunoassay; Immunoblotting; Inflammation; Inherited; Interval training; Ischemia; Manufacturer Name; Measurement; Measures; Mediating; Membrane Proteins; Methodology; Methods; Minor; Mitochondria; Molecular; Molecular Weight; Multiple Trauma; Mus; Mutation; Myocardial Infarction; Orphan; Oxidative Stress; Parkinson Disease; Pathologic; Pathologic Processes; Penicillin-Binding Proteins; Performance; Photoreceptors; Physical Performance; Physiological; Post-Translational Protein Processing; Predictive Analytics; Preparation; Process; Protein Isoforms; Proteins; Proteomics; Quality of life; RNA Interference; Reproducibility; Reproducibility of Results; Research; Research Personnel; Research Project Grants; Retina; Retinal Degeneration; Retinal Dystrophy; Retinitis Pigmentosa; Role; Running; Sampling; Sheep; Signaling Protein; Skeletal Muscle; Therapeutic Agents; Therapeutic Intervention; Time; Tissues; Translational Research; Universities; Validation; Veterans; Western Blotting; Work; antimicrobial; base; bench to bedside; cardiac repair; chemokine; cost; cytokine; dopaminergic neuron; exosome; frailty; healthspan; human model; improved; insight; instrument; macrophage; military veteran; novel; parkin gene/protein; pre-clinical; pre-clinical research; prevent; programs; protein biomarkers; protein expression; receptor; repaired; response; single-cell RNA sequencing; skeletal muscle metabolism; stem cells; targeted treatment; therapeutic candidate; therapy development; visual dysfunction

Project Abstract The Bio-Techne Intracellular and Extracellular Protein Signaling Station (IEPSS) automates standard western blotting and immunoassay and produces reliable, reproducible quantitative data in a very short time. The IEPSS provides a wide array of capabilities, including single cell western blotting, identification of protein isoforms and post-translational modifications in a single cell, separation of proteins based on size and charge, measure four or more analytes in multiple samples. Thus, the IEPSS will provide immediate benefits for VAWNYHS investigators studying the underlying acute and chronic processes that result in physiological dysfunction, disease, and health decline, ultimately permitting the development of interventions to improve the quality of life in the Veteran population. These projects include: Dr. Troen’s research investigates physical performance, frailty, and healthspan during aging and is presently studying the benefits of high intensity interval training (HIIT) for skeletal muscle performance in aging veterans. The IEPSS will allow assessment of protein markers and posttranslational modifications associated with mitochondrial health and skeletal muscle metabolism. Dr. Fliesler’s projects investigate the underlying mechanism of progressive retinal degeneration and visual dysfunction associated with blast overpressure-induced polytrauma, and the impact of novel antioxidants as therapeutic agents to prevent, minimize, or slow the progression of the pathological processes. The IEPSS will afford assessment of biomarkers of inflammation, oxidative stress, and cell death. Dr. Sullivan’s study investigates the development of post-transcriptional gene silencing agents such as ribozymes as candidate therapeutics for orphan retinal degenerations and common age-related macular degeneration. The IEPSS will permit assessment of ribozyme rescue strategy and quantify target protein expression and post-translational modification in photoreceptor and retinal epithelial cells. Dr. Canty’s study investigates cellular remodeling during sudden cardiac arrest and cardiac stem cell mediated repair. The IEPSS will facilitate a proteomic profile of hematopoietic subtypes as well as macrophage subpopulations, also enable to study the chemokines/cytokines. In addition, it quantifies protein changes that arise in response to reversible ischemia. Dr. Feng’s study seeks to identify more efficient methods to understand how mutations of parkin cause the selective degeneration of human dopaminergic neurons and the ensuing Parkinson’s disease. The IEPSS will allow for characterization of protein expression profiles and posttranslational modifications. Dr. Russo’s research seeks to determine the role of penicillin binding protein (PBP) 7/8 as a novel anti- microbial target in XDR A. baumannii. The IEPSS will enable to resolve molecular mechanism of PBP 7/8 and develop receptor-targeted therapies by profiling various outer membrane proteins in single and cultured cells, identifying post-translational modifications in the presence or absence of PBP 7/8. Dr. Farkas’ research seeks to discover potential therapies to prevent and/or treat age-related macular degeneration (AMD) and inherited retinal dystrophies (IRDs). The IEPSS will enable validation of the effects of DNA methylation changes on corresponding protein expression and quantify the cell-to-cell variability of the retinitis pigmentosa 1 minor isoform in the mouse retina. Dr. Lang’s research seeks to determine the functional role of exosomes in stem cell-mediated cardiac repair. The IEPSS will enhance this work by performing multiple immunoassays on small quantities of initial sample and providing the ability to quantify cytokine panels in response to exosome therapy and measuring protein expression in stem cells and in murine cardiac tissue following myocardial infarction.

项目摘要 生物技术细胞内和细胞外蛋白质信号站（IEPSS）自动化 标准的蛋白质印迹和免疫测定法，并在非常可靠的，可再现的定量数据中 短时间。 IEPSS提供了各种能力，包括单细胞蛋白质印迹， 在单个细胞中鉴定蛋白质同工型和翻译后修饰，蛋白质的分离 根据大小和电荷，测量多个样本中的四个或更多分析物。那就是IEPSS提供 Vawnyhs的研究人员的直接利益，研究了基本的急性和慢性过程 导致身体功能障碍，疾病和健康下降，最终允许发展 改善退伍军人人口生活质量的干预措施。这些项目包括： Troen博士的研究调查了衰老期间的身体绩效，脆弱和健康状况 目前正在研究高强度间隔训练（HIIT）的好处 老化的退伍军人。 IEPSS将允许评估蛋白质标记和翻译后修饰 与线粒体健康和骨骼肌代谢相关。 弗莱斯勒博士的项目调查了进行性残余变性的潜在机制和 与爆炸超压诱导的多发性杂志有关的视觉功能障碍以及新颖的影响 抗氧化剂作为治疗剂，可预防，最小化或减慢病理的发展 过程。 IEPS将对炎症，氧化应激和细胞死亡的生物标志物进行评估。 沙利文博士的研究调查了转录后基因沉默剂的发展。 作为核酶作为孤儿视网膜退化和常见年龄相关的黄斑的候选疗法 退化。 IEPSS将允许评估核酶救援策略并量化目标蛋白 光感受器乃至进一步的上皮细胞中的表达和翻译后修饰。 Canty博士的研究研究了心脏骤停和心脏干细胞期间的细胞重塑 介导的维修。 IEPSS将促进造血亚型的蛋白质组学特征以及 巨噬细胞亚群，也可以研究趋化因子/细胞因子。另外，它量化了蛋白质 响应可逆性缺血而产生的变化。 Feng博士的研究旨在确定更有效的方法来了解Parkin的突变 引起人多巴胺能神经元和随后的帕金森氏病的选择性变性。 IEPS将允许表征蛋白质表达谱和翻译后修饰。 Russo博士的研究旨在确定青霉素结合蛋白（PBP）7/8的作用 XDR A. Baumannii中的微生物靶标。 IEPSS将能够解决PBP 7/8的分子机制和 通过在单个和培养的各种外膜蛋白中分析各种外膜蛋白来开发受体靶向的疗法 细胞，在存在或不存在PBP 7/8的情况下识别翻译后修饰。 Farkas博士的研究旨在发现预防和/或治疗与年龄有关的黄斑的潜在疗法 变性（AMD）和遗传性视网膜营养不良（IRD）。 IEPSS将验证效果 DNA甲基化对相应蛋白表达的变化，并量化细胞对细胞变异性 小鼠视网膜的色素性视网膜炎1小同工型。 Lang博士的研究旨在确定外泌体在干细胞介导的心脏中的功能作用 维修。 IEPSS将通过少量初始进行多次免疫测定来增强这项工作 样品并提供对外泌体治疗和测量的量化细胞因子面板的能力 心肌梗塞后干细胞和鼠心脏组织中的蛋白质表达。