Zeiss PALM MicroBeam

描述（由申请人提供）：这是一项在肯塔基州大学使用激光显微切割和压力催化（LMPC）技术建立激光显微切割仪器的提案。激光显微切割技术已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。在英国，许多NIH支持的项目专注于基因和蛋白质表达方法，在许多情况下，明确关注特定的细胞类型，组织病变，遗传修饰位点，甚至亚细胞区域。结合计算机自动化，高选择性的标本采集的能力将大大加快研究进展，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，癌性病变和斑块中组织，细胞和亚细胞区室的细微变化，以及衰老，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疗的概念紧密结合。本文提出的集成系统（Zeiss PALM MicroBeam）具有强大的功能，准确性和灵活性，可满足主要用户在此应用中的各种需求，并将使研究人员能够专注于从现存组织中获得的同质细胞收集。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病理过程中在转录和蛋白质组水平上研究不同细胞类型之间的关键相互作用，从而合理开发新药和个性化病理诊断。因此，拟议中的系统不仅将具体提高在英国的多个NIH资助的项目的进展，但将促进新方法的开发，可能也有利于许多其他机构的研究人员。相关性：近年来，分子测量技术的进展（例如，蛋白质组学、基因表达阵列）已经产生了对疾病过程的重要见解。这里提出的设备将带来采样技术（即，在细胞或甚至亚细胞水平上选择用于研究的组织区域的能力）达到相同的标准。先进的分子分析和细胞水平的收集特异性相结合，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性化的治疗方法。

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.