Core C: Genomics and High Throughput Screening Core

核心 C：基因组学和高通量筛选核心

• 批准号: 8298251
• 负责人: SCOTT L DIAMOND
• 金额: $ 20.16万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8298251
• 关键词: Address; Adherence; Affect; Benign; Binding; Biological Assay; Biology; Blood; Blood Cells; Bone Marrow; Cells; Cellular biology; Chemicals; Commit; Complex; Core Facility; DNA; Defect; Diamond; Dysmyelopoietic Syndromes; Embryo; Endothelial Cells; Environment; Epigenetic Process; Equipment; Erythropoiesis; Faculty; Financial Support; Genes; Genetic Screening; Genetic Transcription; Genomics; Genotype; Goals; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Human; Individual; Investments; Laboratories; Libraries; Liquid substance; MYB gene; Megakaryocytes; Megakaryocytopoieses; Methodology; Microfluidics; Modification; Molecular; Molecular Diagnosis; Molecular Profiling; Monitor; Myelogenous; Neurosciences; Non-Malignant; NuRD complex; Pancytopenia; Pathologic; Pear; Pennsylvania; Pharmaceutical Preparations; Preclinical Drug Evaluation; Price; Process; Proto-Oncogene Proteins c-myb; RNA analysis; Research; Research Personnel; Resources; Running; Screening procedure; Services; Simulate; Small Interfering RNA; Standardization; System; Systems Biology; Technology; Thrombopoiesis; Translating; United States National Institutes of Health; Universities; Work; combinatorial; embryonic stem cell; experience; high throughput screening; inhibitor/antagonist; innovative technologies; interest; member; miniaturize; progenitor; ranpirnase; shear stress; small molecule libraries; stem; tool

This Core provides cutting edge tools that allow invesfigators to monitor cellular and molecular changes that occur during normal hematopoiesis or in pathological states associated with bone marrow failure (BMF), nonmalignant myelodysplastic syndromes or defects in erythropoiesis/megakaryopoiesis, addressing the three foci of this application as detailed in the OVERALL DESCRIPTION. There is a clear need for services to identify and analyze in a rapid, high throughput fashion drugs that influence hematopoiefic cell commitment to various lineages and to develop miniaturized systems for studies of stromal/niche environments. Dr. Diamond is the director of the University of Pennsylvania (UPENN) PCMD, which he established as a Core Facility in 2005 (see BIOSKETCH). Dr. Diamond has 20 years of experience with numerous projects in endothelial biology, blood biology, and blood systems biology. He already has been working with Drs. Poncz, French and Gadue on niche effects on thrombopoiesis from mature megakaryocytes. He will be overall Director and Director of SubCore C-1. Dr. Baldwin will direct the analysis of RNA and DNA changes in cells during hematopoiesis. He has 11 years of industrial and academic experience in microarray assays, serves on the Neuroscience Microarray Consortium Advisory Panel for the NIH, co-chairs the MicroArray Research Group of the Associafion of Biomolecular Resource Facilifies, and interacts regularly with core directors on a nafional level (see BIOSKETCH). Dr. Baldwin founded the Penn Microarray Facility in 2001, was appointed Director of the Molecular Diagnosis and Genotyping Facility in 2005, and has merged the two laboratories to create the Molecular Profiling Facility. He has conducted previous genomic profiling projects with Drs. Weiss, Blobel, Carroll, Diamond, Discher, Gewirtz, June and Pear on efforts directly relevant to this P30. We have combined components of the two UPENN cores run by Drs. Diamond and Baldwin to develop a single core for this P30 to incorporate state-of-the-art resources on our campus that will unite our abilities to analyze normal, pathologic and manipulated hematopoietic cells. SubCore C-1 offers high-throughput microscale screening for compounds that affect various aspects of hematopoiefic cell biology, including lineage commitment (either from embryonic stem (ES) cells or more differentiated progenitors), survival, proliferation or maturafion into mature blood cells. SubCore C-2 will analyze changes that occur in the RNA expression profiles and epigenetic DNA marks in these cells either de novo or after modifications using Core E. We believe that these two SubCores reflect a common theme of rapidly analyzing cells and cellular changes using complex methodologies with significant investment in rapidly changing equipment and technologies. Core C is committed to bringing the most current and innovative technologies to the P30 investigators, while providing campus-wide standardization of services to support cooperafive efforts by different invesfigators with complementary interests and expertise. Our goal is to provide significant labor-intensive service and guidance at very compefitive pricing, supported in part by efficiency of utilizafion and by UPENN financial support.

该核心提供了尖端工具，允许研究者监测正常造血过程中或与骨髓衰竭（BMF）、非恶性骨髓增生异常综合征或红细胞生成/巨核细胞生成缺陷相关的病理状态中发生的细胞和分子变化，解决了总体描述中详述的本申请的三个焦点。显然需要提供服务， 以快速、高通量的方式分析影响造血细胞向各种谱系定型的药物，并开发用于基质/生态位环境研究的小型化系统。Diamond博士是宾夕法尼亚大学（UPENN）PCMD的主任，他于2005年将其作为核心设施建立（见BIOSKETCH）。Diamond博士在内皮生物学、血液学和血液学领域拥有20年的丰富经验。 血液系统生物学。他已经与Poncz，French和Gadue博士合作研究成熟巨核细胞对血小板生成的生态位效应。他将担任SubCore C-1的总体总监和总监。鲍德温博士将指导分析造血过程中细胞中的RNA和DNA变化。他在微阵列分析方面拥有11年的工业和学术经验，在NIH的神经科学微阵列联盟咨询小组任职，担任生物分子资源设施协会微阵列研究组的联合主席，并定期与国家级核心主任互动 (see BIOSKETCH）。Baldwin博士于2001年成立了Penn Microarray Facility，并于2005年被任命为分子诊断和基因分型机构的负责人，并将两个实验室合并为分子分析机构。他曾与韦斯博士、布洛贝尔博士、卡罗尔博士、戴蒙德博士、迪舍尔博士、格茨博士、琼博士和皮尔博士一起进行过与P30直接相关的基因组分析项目。 Diamond和Baldwin为这个P30开发了一个单一的核心，以整合我们校园内最先进的资源，这将使我们能够分析正常，病理和操纵的造血细胞。SubCore C-1为影响造血细胞生物学各个方面的化合物提供高通量微尺度筛选，包括谱系定型（来自胚胎干（ES）细胞或更分化的祖细胞），存活，增殖或成熟为成熟血细胞。SubCore C-2将分析这些细胞中RNA表达谱和表观遗传DNA标记的变化，无论是从头还是使用Core E修饰后。我们认为，这两个子核心反映了一个共同的主题，即使用复杂的方法快速分析细胞和细胞变化，并在快速变化的设备和技术上进行大量投资。核心C致力于为P30研究人员带来最新和最创新的技术，同时提供校园范围内的标准化服务，以支持具有互补兴趣和专业知识的不同研究人员的合作努力。我们的目标是以极具竞争力的价格提供重要的劳动密集型服务和指导，部分由利用效率和UPENN的财政支持支持。