Zeiss PALM MicroBeam

描述(由申请人提供)：这是一项在肯塔基大学使用激光显微解剖和压力弹射(LMPC)技术建立激光显微解剖仪器的建议。激光显微切割技术已经成为许多机构尖端生物医学研究的标准，显然将彻底改变基因和蛋白质表达的研究。英国国立卫生研究院资助的许多项目侧重于基因和蛋白质表达方法，在许多情况下，明确关注特定细胞类型、组织损伤、转基因基因位点，甚至亚细胞区域。将计算机自动化、高度选择性的标本收集结合在一起的能力将极大地加快研究进展，完善解释，并推动在各种生理和病理条件下发现新的机制，这些都是英国研究企业的重点。特别是，英国的主要用户项目强调检测各种细胞类型、癌症病变和斑块中组织、细胞和亚细胞间隔的细微变化，包括衰老、阿尔茨海默病、炎症、创伤性脑损伤、氧化应激和感染，并将翻译目标与个性化医学的概念高度结合起来。这里提出的集成系统(蔡司掌上微束)具有强大的功能、准确性和灵活性，可以满足这一应用中主要用户的不同需求，并将使研究人员能够专注于从现有组织中提取同种细胞。结合英国的分子专业知识，该系统将使我们的研究人员能够在转录和蛋白质组水平上研究病理过程中不同细胞类型之间的关键相互作用，从而导致新药的合理开发和个性化的病理诊断。因此，拟议的系统不仅将特别促进英国国家卫生研究院资助的多个项目的进展，还将促进新方法的开发，这些方法可能也会使许多其他机构的研究人员受益。相关性：近年来，分子测量技术(例如蛋白质组学、基因表达阵列)的进步对疾病过程产生了重要的见解。这里提出的设备将使取样技术(即在细胞或甚至亚细胞水平上选择组织区域进行研究的能力)达到相同的标准。先进的分子分析和细胞水平收集特异性的结合将使我们能够研究不同类型的细胞在阿尔茨海默氏症、癌症和心脏病等疾病中的作用，从而合理开发新药和个体化治疗药物方法。

DESCRIPTION (provided by applicant): This is a proposal to establish laser microdissection instrumentation using Laser Microdissection and Pressure Catapulting (LMPC) technology at the University of Kentucky. Laser microdissection technology has become a standard for cutting-edge biomedical research at many institutions and clearly will revolutionize studies of gene and protein expression. Numerous NIH-supported projects at UK focus on gene and protein expression approaches, in many cases with a clear focus on particular cell types, tissue lesions, genetically modified loci, and even subcellular regions. The ability to incorporate computer-automated, highly selective specimen collection will vastly accelerate research progress, refine interpretation, and drive the discovery of novel mechanisms in various physiological and pathological conditions that are the focus of UK's research enterprise. In particular, major user projects at UK emphasize detection of subtle changes in tissue, cell, and subcellular compartments in various cell types, cancerous lesions, and plaques, with aging, Alzheimer's disease, inflammation, traumatic brain injury, oxidative stress, and infection and heavily integrate translational goals with the concept of personalized medicine. The integrated system proposed here (Zeiss PALM MicroBeam) has the power, accuracy, and flexibility to address the diverse needs of the Major Users in this application and will allow researchers to focus on homogenous cell collection derived from extant tissue. Coupled with the molecular expertise at UK, this system will allow our researchers to investigate the critical interplay among different cell types at the transcriptional and proteomic levels during pathological processes, leading to rational development of new drugs and individualized pathological diagnoses. Thus, the proposed system will not only specifically enhance progress in multiple NIH-funded projects at UK, but will facilitate the development of new methods that may well benefit investigators at many other institutions as well. Relevance: In recent years, advances in molecular measurement technology (e.g., proteomics, gene expression arrays) have yielded important insights into disease processes. The equipment proposed here will bring sampling technology (i.e., the ability to select an area of tissue for study at the cellular or even subcellular level) up to the same standard. The combination of advanced molecular analysis and cell-level collection specificity will allow us to investigate the roles of different kinds of cells in diseases such as Alzheimer's, cancer and heart disease, leading to rational development of new drugs and individualized medicine approaches for treatment.