ShEEP Request for Leica Laser Capture Microdissection System (LMD7)

ShEEP 请求徕卡激光捕获显微切割系统 (LMD7)

• 批准号: 9908938
• 负责人: Gianfranco D Alpini
• 金额: --
• 依托单位: RLR VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908938
• 关键词: Affect; Alcoholic Liver Diseases; Area; Biology; Biomedical Research; Cancer Biology; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cell Culture Techniques; Cell Separation; Cells; Chromosomes; Chronic; Chronic Disease; Cirrhosis; Cloning; Collaborations; Computer software; Data; Diabetes Mellitus; Discipline; Disease; Dissociation; Equipment; Fluorescence; Functional disorder; Funding; Gastroenterology; Genes; Genomic DNA; Goals; Health Benefit; Healthcare; Healthcare Systems; Hepatitis B; Hepatitis C; Hepatology; Human; Indiana; Intracellular Signaling Proteins; Knowledge; Lasers; Lead; Leadership; Light; Liver; Liver Fibrosis; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Maps; Mechanics; Medical; Medical center; Messenger RNA; Metabolic Bone Diseases; Methods; MicroRNAs; Microdissection; Microscope; Molecular; Molecular Analysis; Morbidity - disease rate; Neurologic; Neurosciences; Organ; Pathogenesis; Pathologic; Pathologic Processes; Pathology; Phase; Play; Population; Prevention therapy; Proteomics; Research; Research Personnel; Resolution; Sampling; Science; Sheep; Specimen; Subcellular structure; System; Techniques; Tissue Sample; Tissue Stains; Tissues; Translational Research; United States; Universities; Veterans; animal tissue; bone metabolism; cell type; cholangiocyte; cholestatic liver disease; chronic liver disease; design; diabetic; hazard; human disease; human model; improved; instrument; interest; laser capture microdissection; medical schools; metabolomics; microsystems; mortality; neuropathology; next generation sequencing; non-alcoholic fatty liver disease; novel; novel therapeutics; operation; problem drinker; research facility; single cell analysis; tool; transcriptomics; translational research program; Affect; Alcoholic Liver Diseases; Area; Biology; Biomedical Research; Cancer Biology; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cell Culture Techniques; Cell Separation; Cells; Chromosomes; Chronic; Chronic Disease; Cirrhosis; Cloning; Collaborations; Computer software; Data; Diabetes Mellitus; Discipline; Disease; Dissociation; Equipment; Fluorescence; Functional disorder; Funding; Gastroenterology; Genes; Genomic DNA; Goals; Health Benefit; Healthcare; Healthcare Systems; Hepatitis B; Hepatitis C; Hepatology; Human; Indiana; Intracellular Signaling Proteins; Knowledge; Lasers; Lead; Leadership; Light; Liver; Liver Fibrosis; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Maps; Mechanics; Medical; Medical center; Messenger RNA; Metabolic Bone Diseases; Methods; MicroRNAs; Microdissection; Microscope; Molecular; Molecular Analysis; Morbidity - disease rate; Neurologic; Neurosciences; Organ; Pathogenesis; Pathologic; Pathologic Processes; Pathology; Phase; Play; Population; Prevention therapy; Proteomics; Research; Research Personnel; Resolution; Sampling; Science; Sheep; Specimen; Subcellular structure; System; Techniques; Tissue Sample; Tissue Stains; Tissues; Translational Research; United States; Universities; Veterans; animal tissue; bone metabolism; cell type; cholangiocyte; cholestatic liver disease; chronic liver disease; design; diabetic; hazard; human disease; human model; improved; instrument; interest; laser capture microdissection; medical schools; metabolomics; microsystems; mortality; neuropathology; next generation sequencing; non-alcoholic fatty liver disease; novel; novel therapeutics; operation; problem drinker; research facility; single cell analysis; tool; transcriptomics; translational research program

Laser Microdissection LMD7 System enables users to isolate specific single cells or entire areas of tissue. This system allows rapid and accurate microdissection of both small and large groups of cells and can be used with phase contrast for live-cell applications, with stained tissue samples and transmitted light, or with epi- fluorescence for fluorescence tagged targets. Powered by a unique laser design and dynamic software, Leica LMD7 systems allow users to easily isolate Regions of Interest (ROI) from entire areas of tissue down to single cells or even subcellular structures such as chromosomes. Our VA researchers in hepatology, gastroenterology, cholangiocytes biology and diabetic pathology rely on this method. Furthermore, LMD7 system is a perfect tool for live cell culture (LCC), for cloning and re-cultivation, manipulation or downstream analysis. At the Richard L. Roudebush VA Medical Center (RRVA) at Indianapolis, increased interactions and collaborations have been established among multiple investigators with expertise in liver and cholangiocytes pathobiology, neuropathology, cancer biology, cardiovascular pathophysiology, diabetes and bone metabolism. With the purchase of the shared equipment of the Leica Laser Capture Microdissection system LMD7, which can be used by investigators of different disciplines for the single cell analysis in human healthy and diseased tissues and cells, such collaborations could be further enhanced. Several of the proposed users are focused on chronic liver disorders such as alcoholic liver diseases; Non-alcoholic fatty liver disease (NAFLD), cholestatic liver diseases, hepatitis B and C virus infections are severe medical disorders and will further develop to liver fibrosis, cirrhosis and liver cancer. They are the 10th leading cause of death in the United States that are highly relevant to our veterans. The study shows that the hazard of developing chronic liver diseases and liver cancer cirrhosis in the VA health care system significantly increased recently. The translational research approach of the healthy and diseases human liver at single-cell resolution is critical to understanding the pathogenesis and treatment of human liver disease. This single cell analysis approach has been difficult to carry out, mainly because fresh human liver tissue access is scarce and the tissue is difficult to fractionate without damaging fragile resident cell populations. Cells and tissues from animals and humans that model various pathological processes have played a vital part in medical breakthroughs in the past decade that have benefited the health care of US populations including Veterans. The Leica Laser Capture Microdissection System LMD7 requested in this application will be used to study intracellular signaling and protein interactions in single human cell stage under pathological conditions of human liver and other diseases that lead to significant mortality and morbidity in the Veteran population. The long-term objective of the investigators involved in this application is to obtain a better understanding of molecular underpinnings of diseases with the ultimate goal of improving healthcare for Veterans. The requested Leica Laser Capture Microdissection LMD7 system is critical for progress in these important areas. Two specific aims are proposed in this application: Aim 1: To purchase and maintain a Leica LMD7 system for use by dedicated VA researchers. Aim 2: To enhance the quality of science and promote collaboration among dedicated VA researchers. Results of this proposed research will provide a better understanding of underlying mechanisms critical for designing new therapies for the prevention and treatment of these chronic human diseases. The Leica LMD7 system makes it possible to generate the gene profiling data at specific cell type of intact specimens. It also becomes possible to exclude incorrect results caused by mechanically isolation of the cells from the samples. Having this novel, state-of-the-art laser capture microdissection system will open up new avenues of research and collaboration at RRVA that will not be possible without it.

激光显微解剖LMD7系统使用户能够分离特定的单细胞或整个组织区域。这 系统可以快速准确地对小组和大型单元组进行微解析，可以与 活细胞应用，带有染色的组织样品和发射光的相比对比，或 荧光标记目标的荧光。由独特的激光设计和动态软件提供动力，Leica LMD7系统允许用户轻松地将感兴趣的区域（ROI）从整个组织区域隔离到单个区域 细胞甚至亚细胞结构，例如染色体。我们的VA肝病学研究人员，胃肠病学， 胆管细胞生物学和糖尿病病理学依赖于这种方法。此外，LMD7系统是一个完美的工具 用于活细胞培养（LCC），用于克隆和重新培养，操纵或下游分析。在理查德 印第安纳波利斯的L. Roudebush VA医疗中心（RRVA），互动和合作增加了 在多个具有专业知识的研究人员中建立的肝脏和胆管细胞病理学， 神经病理学，癌症生物学，心血管病理生理学，糖尿病和骨代谢。与 购买Leica Laser Capture Microdesection System LMD7的共享设备，可以使用 由不同学科的研究者进行人类健康和患病组织中的单细胞分析以及 细胞，这种合作可以进一步增强。一些建议的用户专注于慢性肝脏 诸如酒精肝疾病之类的疾病；非酒精性脂肪肝疾病（NAFLD），胆汁淤积性肝病， 丙型肝炎和C病毒感染是严重的医学疾病，将进一步发展为肝纤维化， 肝硬化和肝癌。他们是美国高度相关的第十个主要死亡原因 给我们的退伍军人。研究表明，患上慢性肝病和肝癌肝硬化的危害 在VA中，医疗保健系统最近大大增加了。转化研究方法 在单细胞分辨率下，健康和疾病的人肝脏对于理解发病机理和 治疗人肝病。这种单细胞分析方法很难进行，主要是 因为新鲜的人肝组织进入是稀缺的，并且组织难以分割而不会损害 脆弱的居民细胞种群。动物和人类的细胞和组织，模拟各种病理 在过去的十年中，过程在医学突破中起着至关重要的作用，这使健康受益 照顾包括退伍军人在内的美国人口。请求的Leica激光捕获微解剖系统LMD7 在此应用中，将使用单个人类细胞中的细胞内信号传导和蛋白质相互作用 在人类肝脏的病理状况和其他疾病的病理状况下，导致重大死亡和 退伍军人人口的发病率。参与此应用程序的调查人员的长期目标是 为了更好地了解疾病的分子基础，其最终目标是改善 退伍军人的医疗保健。请求的Leica Laser Capture Microdection LMD7系统对于 在这些重要领域的进展。在此应用程序中提出了两个具体目标：目标1：购买和 维护LEICA LMD7系统，可供专门的VA研究人员使用。目标2：提高科学质量 并促进敬业的VA研究人员之间的合作。这项拟议研究的结果将提供 更好地了解针对预防新疗法至关重要的基本机制 治疗这些慢性人类疾病。 Leica LMD7系统使生成基因成为可能 在特定细胞类型的完整标本中分析数据。也可以排除错误的结果 由样品中细胞机械分离引起。拥有这本小说，最先进的激光捕获 微分解系统将在RRVA开放新的研究与协作途径 没有它。